Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IBA GO_REF:0000033	ACCEPT	Summary: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0042981 regulation of apoptotic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: regulation of apoptotic process is a broad downstream p53 cell-fate annotation rather than the core Trp53 molecular function. Reason: p53 can induce apoptotic programs after stress, but broad apoptosis terms should be retained as non-core because the core Trp53 function is sequence-specific DNA-binding transcriptional regulation. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Canonical apoptotic targets include Bbc3/Puma, Bax, Pmaip1/Noxa, and Apaf1.
GO:1990841 promoter-specific chromatin binding	IBA GO_REF:0000033	ACCEPT	Summary: promoter-specific chromatin binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0045944 positive regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: positive regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0000785 chromatin	IBA GO_REF:0000033	ACCEPT	Summary: chromatin is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0000976 transcription cis-regulatory region binding	IEA GO_REF:0000120	ACCEPT	Summary: transcription cis-regulatory region binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0003677 DNA binding	IEA GO_REF:0000120	ACCEPT	Summary: DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000120	ACCEPT	Summary: DNA-binding transcription factor activity is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005737 cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: cytoplasm is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: mitochondrial matrix is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: endoplasmic reticulum is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005813 centrosome	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: centrosome is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000120	ACCEPT	Summary: regulation of DNA-templated transcription is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0006915 apoptotic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: apoptotic process is a broad downstream p53 cell-fate annotation rather than the core Trp53 molecular function. Reason: p53 can induce apoptotic programs after stress, but broad apoptosis terms should be retained as non-core because the core Trp53 function is sequence-specific DNA-binding transcriptional regulation. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Canonical apoptotic targets include Bbc3/Puma, Bax, Pmaip1/Noxa, and Apaf1.
GO:0006979 response to oxidative stress	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: response to oxidative stress is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: response to xenobiotic stimulus is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0009411 response to UV	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: response to UV is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0010165 response to X-ray	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: response to X-ray is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0016605 PML body	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: PML body is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0048468 cell development	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: cell development is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0051053 negative regulation of DNA metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: negative regulation of DNA metabolic process is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0051262 protein tetramerization	IEA GO_REF:0000002	ACCEPT	Summary: protein tetramerization is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0097190 apoptotic signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: apoptotic signaling pathway is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0097371 MDM2/MDM4 family protein binding	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: MDM2/MDM4 family protein binding is a valid p53 regulatory interaction, but it belongs outside the core function set. Reason: Retain as non-core because MDM2/MDM4 binding controls p53 stability and activity, whereas the core Trp53 function is sequence-specific transcriptional regulation of stress-response targets. Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. file:mouse/Trp53/Trp53-deep-research-falcon.md MDM4/MDMX restrains p53 transactivation and forms a heterodimer with MDM2 to enhance p53 degradation.
GO:2001242 regulation of intrinsic apoptotic signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: regulation of intrinsic apoptotic signaling pathway is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005515 protein binding	IPI PMID:10329544 Hepatitis C virus core protein interacts with a human DEAD b...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:11181729 The AKT3 potassium channel protein interacts with the AtPP2C...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:11274052 Naked cuticle targets dishevelled to antagonize Wnt signal t...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:11781573 Design and application of a cytokine-receptor-based interact...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:16151013 PUMA couples the nuclear and cytoplasmic proapoptotic functi...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:16480949 The intracellular domain of amyloid precursor protein intera...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:16697373 Interaction of nucleoside diphosphate kinase and catalases f...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:17535810 Functional similarity between the chloroplast translocon com...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:17936560 Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligas...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:18025262 Interaction between transcription factor, basal transcriptio...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:18303029 BAF60a interacts with p53 to recruit the SWI/SNF complex.	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:18359851 Hedgehog signaling overrides p53-mediated tumor suppression ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:18448518 The nucleocapsid protein of severe acute respiratory syndrom...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:18695251 AIMP2/p38, the scaffold for the multi-tRNA synthetase comple...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:19011633 Bach1 inhibits oxidative stress-induced cellular senescence ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:19556538 Trim24 targets endogenous p53 for degradation.	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:20621096 Deletion of Swm2p selectively impairs trimethylation of snRN...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:20697359 Regulation of MDM4 (MDMX) function by p76(MDM2): a new facet...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:20708612 DJ-1, an oncogene and causative gene for familial Parkinson'...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:20832751 An ARF-independent c-MYC-activated tumor suppression pathway...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:21057544 p85α mediates p53 K370 acetylation by p300 and regulates its...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:21122074 Interaction of Sesbania mosaic virus movement protein with t...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:21670284 Near-UV cyanobacteriochrome signaling system elicits negativ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:21741598 A Pin1/mutant p53 axis promotes aggressiveness in breast can...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:21857681 A stress response pathway regulates DNA damage through β2-ad...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:21909133 Manganese superoxide dismutase is a mitochondrial fidelity p...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:22056770 Structural basis for the molecular evolution of SRP-GTPase a...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:22726440 p53 opens the mitochondrial permeability transition pore to ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:23123091 Involvement of PTEN in TPA-mediated p53-activation in mouse ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:23980194 E258K HCM-causing mutation in cardiac MyBP-C reduces contrac...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:24116158 The nuclear envelope protein, LAP1B, is a novel protein phos...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:25117711 Regulation of p53 by Mdm2 E3 ligase function is dispensable ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:26960425 Yeast Two-Hybrid Screening for Proteins that Interact with t...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:28536627 The identification of human aldo-keto reductase AKR7A2 as a ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:37025149 Arabidopsis LFR, a SWI/SNF complex component, interacts with...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005515 protein binding	IPI PMID:9194565 Binding and modulation of p53 by p300/CBP coactivators.	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0000122 negative regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	ACCEPT	Summary: negative regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0000785 chromatin	IEA GO_REF:0000107	ACCEPT	Summary: chromatin is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IEA GO_REF:0000107	ACCEPT	Summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0000987 cis-regulatory region sequence-specific DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: cis-regulatory region sequence-specific DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0001046 core promoter sequence-specific DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: core promoter sequence-specific DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0001094 TFIID-class transcription factor complex binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: TFIID-class transcription factor complex binding is a documented p53 regulatory interaction, but not the core Trp53 molecular function. Reason: Retain as non-core because p53 is primarily curated here as a sequence-specific DNA-binding transcription factor; TFIID/TAF binding is a cofactor interaction that modulates transcriptional regulation. Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex.
GO:0001223 transcription coactivator binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: transcription coactivator binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific	IEA GO_REF:0000107	ACCEPT	Summary: DNA-binding transcription repressor activity, RNA polymerase II-specific is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific	IEA GO_REF:0000107	ACCEPT	Summary: DNA-binding transcription activator activity, RNA polymerase II-specific is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0002020 protease binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: protease binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0002039 p53 binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: p53 binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0002244 hematopoietic progenitor cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: hematopoietic progenitor cell differentiation is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0003682 chromatin binding	IEA GO_REF:0000107	ACCEPT	Summary: chromatin binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0003730 mRNA 3'-UTR binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: mRNA 3'-UTR binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005507 copper ion binding	IEA GO_REF:0000107	MODIFY	Summary: Copper ion binding is not supported for mouse p53 by the cited evidence; UniProt documents Zn(2+) binding instead. Reason: Replace the unsupported copper-binding term with GO:0008270 zinc ion binding, the metal cofactor documented for p53. Proposed replacements: zinc ion binding Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.
GO:0005654 nucleoplasm	IEA GO_REF:0000120	ACCEPT	Summary: nucleoplasm is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005667 transcription regulator complex	IEA GO_REF:0000107	ACCEPT	Summary: transcription regulator complex is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005730 nucleolus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: nucleolus is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005739 mitochondrion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: mitochondrion is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005829 cytosol	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: cytosol is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0006289 nucleotide-excision repair	IEA GO_REF:0000107	ACCEPT	Summary: nucleotide-excision repair is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0006357 regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	ACCEPT	Summary: regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0006914 autophagy	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: autophagy is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0007265 Ras protein signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ras protein signal transduction is not the direct molecular activity of p53. It may reflect downstream pathway crosstalk from stress and proliferation programs, but it overstates the core p53 function. Reason: p53 is a sequence-specific transcription factor and stress-response regulator. A broad Ras signaling annotation is too pathway-level and indirect for the available evidence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0008104 intracellular protein localization	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Intracellular protein localization is an inferred broad process annotation. p53 itself is regulated by MDM2-mediated nuclear export and stress-dependent nuclear accumulation, but this does not make protein-localization control a core p53 output. Reason: The evidence supports p53 subcellular regulation, not a direct core role for p53 in intracellular protein localization. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Functionally, p53 acts predominantly in the nucleus as a transcription factor. Consistent with this, MDM2-mediated regulation explicitly includes export of nuclear p53 to the cytoplasm, and stress-dependent disruption of this repression allows nuclear accumulation and transcriptional activation. file:mouse/Trp53/Trp53-uniprot.txt GO; GO:0008104; P:intracellular protein localization; ISO:GO_Central.
GO:0008285 negative regulation of cell population proliferation	IEA GO_REF:0000107	ACCEPT	Summary: negative regulation of cell population proliferation is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0009299 mRNA transcription	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: mRNA transcription is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0010332 response to gamma radiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: response to gamma radiation is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0010628 positive regulation of gene expression	IEA GO_REF:0000107	ACCEPT	Summary: positive regulation of gene expression is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0016032 viral process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: viral process is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0016363 nuclear matrix	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: nuclear matrix is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0016604 nuclear body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: nuclear body is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0019899 enzyme binding	IEA GO_REF:0000107	REMOVE	Summary: enzyme binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0030308 negative regulation of cell growth	IEA GO_REF:0000107	ACCEPT	Summary: negative regulation of cell growth is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0030330 DNA damage response, signal transduction by p53 class mediator	IEA GO_REF:0000107	ACCEPT	Summary: DNA damage response, signal transduction by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0030971 receptor tyrosine kinase binding	IEA GO_REF:0000107	REMOVE	Summary: Receptor tyrosine kinase binding is not supported as a direct retained p53 molecular function in the reviewed evidence. UniProt notes many p53 regulatory interactions, including non-receptor PTK2/PTK2B contexts, but not a well-supported receptor tyrosine kinase binding activity. Reason: The annotation appears to be an over-propagated generic binding claim. It is not justified by the Falcon synthesis or UniProt evidence for p53's core DNA-binding transcription factor activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity. file:mouse/Trp53/Trp53-uniprot.txt Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2. Interacts with PTK2B/PYK2.
GO:0031571 mitotic G1 DNA damage checkpoint signaling	IEA GO_REF:0000107	ACCEPT	Summary: mitotic G1 DNA damage checkpoint signaling is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0031625 ubiquitin protein ligase binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Ubiquitin protein ligase binding is a valid non-core regulatory interaction for p53 stability control. Reason: p53 binding to E3 ligases such as MDM2 and FATS regulates p53 stability, but this is regulatory context rather than the core p53 transcription factor activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md MDM2 is a major negative regulator; it ubiquitinates p53 to maintain low basal levels. file:mouse/Trp53/Trp53-uniprot.txt Interacts with C10orf90/FATS; the interaction inhibits binding of TP53 and MDM2.
GO:0032211 negative regulation of telomere maintenance via telomerase	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of telomere maintenance via telomerase is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0032991 protein-containing complex	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: protein-containing complex is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0033209 tumor necrosis factor-mediated signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: tumor necrosis factor-mediated signaling pathway is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0034644 cellular response to UV	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to UV is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0036310 ATP-dependent DNA/DNA annealing activity	IEA GO_REF:0000107	REMOVE	Summary: ATP-dependent DNA/DNA annealing activity is not supported by the reviewed mouse p53 evidence. Reason: The evidence supports sequence-specific DNA binding and transcriptional regulation, not ATP-dependent DNA annealing enzyme activity.
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IEA GO_REF:0000107	ACCEPT	Summary: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0042802 identical protein binding	IEA GO_REF:0000107	ACCEPT	Summary: identical protein binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0042826 histone deacetylase binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Histone deacetylase binding is present as an orthology-derived interaction annotation and fits p53 post-translational regulation by deacetylases such as SIRT1, but it is not the core Trp53 molecular function. Reason: Retain as a supported regulatory interaction context rather than treating histone deacetylase binding as a core p53 function. Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Deacetylation of Lys-379 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence. file:mouse/Trp53/Trp53-uniprot.txt GO; GO:0042826; F:histone deacetylase binding; ISO:GO_Central.
GO:0043065 positive regulation of apoptotic process	IEA GO_REF:0000120	ACCEPT	Summary: positive regulation of apoptotic process is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0043066 negative regulation of apoptotic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Negative regulation of apoptotic process is an inferred annotation that does not match the main p53 apoptotic program; p53 is better supported as a positive regulator of intrinsic apoptosis through targets such as Puma/Bbc3, Bax, Noxa, and Apaf1. Reason: The cited support favors p53-induced apoptosis, not a core anti-apoptotic role for Trp53. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Canonical apoptotic targets include Bbc3/Puma, Bax, Pmaip1/Noxa, and Apaf1. Mouse studies show PUMA is essential for many p53-induced apoptotic responses, while p21 is critical for arrest/senescence. file:mouse/Trp53/Trp53-uniprot.txt GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
GO:0045815 transcription initiation-coupled chromatin remodeling	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: transcription initiation-coupled chromatin remodeling is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0045892 negative regulation of DNA-templated transcription	IEA GO_REF:0000107	ACCEPT	Summary: negative regulation of DNA-templated transcription is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0045893 positive regulation of DNA-templated transcription	IEA GO_REF:0000107	ACCEPT	Summary: positive regulation of DNA-templated transcription is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0045899 positive regulation of RNA polymerase II transcription preinitiation complex assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of RNA polymerase II transcription preinitiation complex assembly is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0046677 response to antibiotic	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Response to antibiotic is a broad treatment-response phenotype, not a direct p53 molecular function. Reason: This can be retained as a context-specific stress-response output, but it should not be core for Trp53. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent.
GO:0046982 protein heterodimerization activity	IEA GO_REF:0000107	REMOVE	Summary: Protein heterodimerization activity is not supported as a direct p53 activity; p53 forms homodimers and homotetramers. Reason: The reviewed evidence supports p53 homodimerization/homotetrameric DNA binding rather than heterodimerization. Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Forms homodimers and homotetramers. Binds DNA as a homotetramer.
GO:0048147 negative regulation of fibroblast proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of fibroblast proliferation is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0048539 bone marrow development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: bone marrow development is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0051087 protein-folding chaperone binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: protein-folding chaperone binding is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0051721 protein phosphatase 2A binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: protein phosphatase 2A binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0051726 regulation of cell cycle	IEA GO_REF:0000107	ACCEPT	Summary: regulation of cell cycle is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0060218 hematopoietic stem cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: hematopoietic stem cell differentiation is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: RNA polymerase II-specific DNA-binding transcription factor binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0065003 protein-containing complex assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: protein-containing complex assembly is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0071456 cellular response to hypoxia	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: cellular response to hypoxia is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0071466 cellular response to xenobiotic stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to xenobiotic stimulus is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0071479 cellular response to ionizing radiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to ionizing radiation is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0071480 cellular response to gamma radiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to gamma radiation is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0072331 signal transduction by p53 class mediator	IEA GO_REF:0000107	ACCEPT	Summary: signal transduction by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator	IEA GO_REF:0000107	ACCEPT	Summary: intrinsic apoptotic signaling pathway by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0072717 cellular response to actinomycin D	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cellular response to actinomycin D is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0090200 positive regulation of release of cytochrome c from mitochondria	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of release of cytochrome c from mitochondria is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0090398 cellular senescence	IEA GO_REF:0000107	ACCEPT	Summary: cellular senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0090399 replicative senescence	IEA GO_REF:0000107	ACCEPT	Summary: replicative senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0090403 oxidative stress-induced premature senescence	IEA GO_REF:0000107	ACCEPT	Summary: oxidative stress-induced premature senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0097252 oligodendrocyte apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Oligodendrocyte apoptotic process is a tissue-specific p53 apoptotic output, not the core Trp53 molecular function. Reason: Retain as non-core because p53 apoptotic programs are highly tissue- and stress-specific; the core activity is DNA-binding transcriptional regulation of cell-fate targets. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Tissue specificity / localization of function \| p53 functions predominantly in the nucleus as a transcription factor, but outputs are markedly cell- and tissue-specific.
GO:0097718 disordered domain specific binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: disordered domain specific binding is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0140296 general transcription initiation factor binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: general transcription initiation factor binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0140677 molecular function activator activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: molecular function activator activity is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0140693 molecular condensate scaffold activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Molecular condensate scaffold activity has UniProt support through p53 condensate regulation, but it is specialized regulatory biophysics rather than the core annotation. Reason: Retain as non-core because phase-separation behavior modulates p53 regulation while the main curated function remains DNA-binding transcriptional control. Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Phosphorylation at Ser-389 regulates its ability to undergo liquid-liquid phase separation by increasing fluidity of TP53/p53 condensates
GO:1900119 positive regulation of execution phase of apoptosis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of execution phase of apoptosis is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:1902895 positive regulation of miRNA transcription	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of miRNA transcription is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:1903451 negative regulation of G1 to G0 transition	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: negative regulation of G1 to G0 transition is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:1905856 negative regulation of pentose-phosphate shunt	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Negative regulation of the pentose-phosphate shunt is supported by a specific G6PD-containing complex, but it is a specialized metabolic branch of p53 activity. Reason: Retain as non-core because this metabolic regulation is context-specific and downstream of p53 regulatory interactions rather than the central DNA-binding transcription factor function. Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Forms a ternary complex with ALDOB and G6PD; this interaction is direct. ALDOB stabilizes the complex inhibiting G6PD activity and keeping oxidative pentose phosphate metabolism in check. file:mouse/Trp53/Trp53-deep-research-falcon.md Metabolic targets include GLS2 and SCO2 (promote OXPHOS) and repression of GLUT1/GLUT4.
GO:1990841 promoter-specific chromatin binding	IEA GO_REF:0000107	ACCEPT	Summary: promoter-specific chromatin binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:2000379 positive regulation of reactive oxygen species metabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of reactive oxygen species metabolic process is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:2000774 positive regulation of cellular senescence	IEA GO_REF:0000107	ACCEPT	Summary: positive regulation of cellular senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: positive regulation of intrinsic apoptotic signaling pathway is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0140693 molecular condensate scaffold activity	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Molecular condensate scaffold activity has UniProt support through p53 condensate regulation, but it is specialized regulatory biophysics rather than the core annotation. Reason: Retain as non-core because phase-separation behavior modulates p53 regulation while the main curated function remains DNA-binding transcriptional control. Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Phosphorylation at Ser-389 regulates its ability to undergo liquid-liquid phase separation by increasing fluidity of TP53/p53 condensates
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:16407291 Endoplasmic reticulum stress-induced apoptosis: multiple pat...	ACCEPT	Summary: p53 positively regulates transcription of PUMA and NOXA during ER stress in MEFs. Reason: PMID:16407291 directly supports p53-dependent transcriptional activation of pro-apoptotic targets in this context. Supporting Evidence: PMID:16407291 ER stress selectively activates BH3-only proteins PUMA and NOXA at the transcript level through the tumor suppressor gene p53.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISS PMID:30089260 p53 Regulates the Expression of LRP1 and Apoptosis through a...	ACCEPT	Summary: positive regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis. Supporting Evidence: PMID:30089260 LRP1 transcript expression is upregulated in response to both sub-lethal and lethal doses of p53-activating stress
GO:0006357 regulation of transcription by RNA polymerase II	ISS PMID:30089260 p53 Regulates the Expression of LRP1 and Apoptosis through a...	ACCEPT	Summary: regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis. Supporting Evidence: PMID:30089260 Our results define a negative feedback loop involving the p53-regulated coding gene LRP1 and p53-regulated miRNA genes.
GO:0006974 DNA damage response	ISS PMID:30089260 p53 Regulates the Expression of LRP1 and Apoptosis through a...	ACCEPT	Summary: DNA damage response is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis. Supporting Evidence: PMID:30089260 LRP1 transcript expression is upregulated in response to both sub-lethal and lethal doses of p53-activating stress
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-9816449	ACCEPT	Summary: nucleoplasm is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:2000774 positive regulation of cellular senescence	IMP PMID:10562313 A proinflammatory cytokine inhibits p53 tumor suppressor act...	ACCEPT	Summary: positive regulation of cellular senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0090398 cellular senescence	ISS GO_REF:0000024	ACCEPT	Summary: cellular senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0036310 ATP-dependent DNA/DNA annealing activity	ISS GO_REF:0000024	REMOVE	Summary: ATP-dependent DNA/DNA annealing activity is not supported by the reviewed mouse p53 evidence. Reason: The evidence supports sequence-specific DNA binding and transcriptional regulation, not ATP-dependent DNA annealing enzyme activity.
GO:0000785 chromatin	ISS PMID:30089260 p53 Regulates the Expression of LRP1 and Apoptosis through a...	ACCEPT	Summary: chromatin is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis. Supporting Evidence: PMID:30089260 Here, we identify low-density lipoprotein receptor-related protein 1 (LRP1), a transmembrane endocytic receptor, as a p53 target gene.
GO:0005813 centrosome	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: centrosome is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0043065 positive regulation of apoptotic process	ISS GO_REF:0000024	ACCEPT	Summary: positive regulation of apoptotic process is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005634 nucleus	IDA PMID:15532030 Coexpression of Brn-3a POU protein with p53 in a population ...	ACCEPT	Summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway	ISS GO_REF:0000024	ACCEPT	Summary: positive regulation of intrinsic apoptotic signaling pathway is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0062100 positive regulation of programmed necrotic cell death	IMP PMID:27258785 The long noncoding RNA NRF regulates programmed necrosis and...	KEEP AS NON CORE	Summary: PMID:27258785 supports p53-dependent promotion of programmed necrosis in cardiomyocytes through the NRF-miR-873-RIPK1/RIPK3 axis. Reason: Retain as non-core because this is a cardiomyocyte ischemia/reperfusion output of p53 transcriptional regulation rather than the general core Trp53 function. Supporting Evidence: PMID:27258785 P53 regulates cardiomyocytes necrosis and myocardial I/R injury through NRF and miR-873. file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:24240685 FATS is an E2-independent ubiquitin ligase that stabilizes p...	KEEP AS NON CORE	Summary: Ubiquitin protein ligase binding is a valid non-core regulatory interaction for p53 stability control. Reason: p53 binding to E3 ligases such as MDM2 and FATS regulates p53 stability, but this is regulatory context rather than the core p53 transcription factor activity. Supporting Evidence: PMID:24240685 FATS acts as a p53 activator by inhibiting Mdm2 binding to p53 file:mouse/Trp53/Trp53-deep-research-falcon.md MDM2 is a major negative regulator; it ubiquitinates p53 to maintain low basal levels. file:mouse/Trp53/Trp53-uniprot.txt Interacts with C10orf90/FATS; the interaction inhibits binding of TP53 and MDM2.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA PMID:24051492 p53 regulates Period2 expression and the circadian clock.	ACCEPT	Summary: PMID:24051492 directly links p53 to Per2 promoter binding, transcriptional repression, and mouse circadian behavior. Reason: PMID:24051492 directly supports p53 binding to the Per2 promoter and repression of BMAL1/CLOCK-mediated Per2 transcription. Supporting Evidence: PMID:24051492 p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK. PMID:24051492 The p53−/− mouse period lengths were 22.8 ± 0.1 h
GO:1990841 promoter-specific chromatin binding	ISS GO_REF:0000024	ACCEPT	Summary: promoter-specific chromatin binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IDA PMID:16213212 Regulation of p53 translation and induction after DNA damage...	ACCEPT	Summary: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0071479 cellular response to ionizing radiation	IDA PMID:16213212 Regulation of p53 translation and induction after DNA damage...	KEEP AS NON CORE	Summary: cellular response to ionizing radiation is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005515 protein binding	IPI PMID:22262176 Ribosomal stress induces L11- and p53-dependent apoptosis in...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0005634 nucleus	IDA PMID:22262176 Ribosomal stress induces L11- and p53-dependent apoptosis in...	ACCEPT	Summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0045892 negative regulation of DNA-templated transcription	IMP PMID:23629966 Deacetylation of p53 induces autophagy by suppressing Bmf ex...	ACCEPT	Summary: negative regulation of DNA-templated transcription is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis. Supporting Evidence: PMID:23629966 p53 also suppressed Bmf expression in response to other cell death-stimulating agents, including ultraviolet radiation and histone deacetylase inhibitors.
GO:0060333 type II interferon-mediated signaling pathway	IMP PMID:23629966 Deacetylation of p53 induces autophagy by suppressing Bmf ex...	KEEP AS NON CORE	Summary: type II interferon-mediated signaling pathway is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005634 nucleus	IDA PMID:16407291 Endoplasmic reticulum stress-induced apoptosis: multiple pat...	ACCEPT	Summary: The PMID:16407291 MEF evidence directly reports nuclear p53 during ER stress. Reason: This supports nuclear localization in the context of the ER-stress apoptotic response. Supporting Evidence: PMID:16407291 In multiple MEF lines, p53 is primarily nuclear and its level is elevated upon ER stress.
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	IMP PMID:16407291 Endoplasmic reticulum stress-induced apoptosis: multiple pat...	ACCEPT	Summary: ER stress-induced apoptosis is directly supported in MEFs and is partially p53-dependent through PUMA and NOXA activation. Reason: PMID:16407291 shows p53 contributes to ER stress-induced apoptosis by transcriptionally activating PUMA and NOXA in MEFs. Supporting Evidence: PMID:16407291 In p53(-/-) MEFs, ER stress-induced apoptosis is partially suppressed.
GO:0007623 circadian rhythm	IEP PMID:24051492 p53 regulates Period2 expression and the circadian clock.	KEEP AS NON CORE	Summary: PMID:24051492 directly links p53 to Per2 promoter binding, transcriptional repression, and mouse circadian behavior. Reason: The paper supports p53 influence on circadian rhythm behavior, but this is a context-specific organismal output, not core molecular function. Supporting Evidence: PMID:24051492 p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK. PMID:24051492 The p53−/− mouse period lengths were 22.8 ± 0.1 h
GO:0043153 entrainment of circadian clock by photoperiod	IMP PMID:24051492 p53 regulates Period2 expression and the circadian clock.	KEEP AS NON CORE	Summary: PMID:24051492 supports altered light-cue phase-shift behavior in p53-null mice, downstream of p53 repression of Per2. Reason: Retain as non-core because the light-entrainment phenotype is an organismal circadian output, while the direct p53 activity is promoter binding and transcriptional repression. Supporting Evidence: PMID:24051492 phase shift response to a light cue displays an enhanced phase delay response during free running conditions PMID:24051492 p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK.
GO:0045892 negative regulation of DNA-templated transcription	IDA PMID:24051492 p53 regulates Period2 expression and the circadian clock.	ACCEPT	Summary: PMID:24051492 directly links p53 to Per2 promoter binding, transcriptional repression, and mouse circadian behavior. Reason: PMID:24051492 directly supports p53 binding to the Per2 promoter and repression of BMAL1/CLOCK-mediated Per2 transcription. Supporting Evidence: PMID:24051492 p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK. PMID:24051492 The p53−/− mouse period lengths were 22.8 ± 0.1 h
GO:0048512 circadian behavior	IMP PMID:24051492 p53 regulates Period2 expression and the circadian clock.	KEEP AS NON CORE	Summary: PMID:24051492 directly links p53 to Per2 promoter binding, transcriptional repression, and mouse circadian behavior. Reason: The paper supports altered circadian behavior in p53-null mice, but this is a context-specific phenotype, not core molecular function. Supporting Evidence: PMID:24051492 p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK. PMID:24051492 The p53−/− mouse period lengths were 22.8 ± 0.1 h
GO:0005739 mitochondrion	IDA PMID:12667443 p53 has a direct apoptogenic role at the mitochondria.	KEEP AS NON CORE	Summary: mitochondrion is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0097252 oligodendrocyte apoptotic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Oligodendrocyte apoptotic process is a tissue-specific p53 apoptotic output, not the core Trp53 molecular function. Reason: Retain as non-core because p53 apoptotic programs are highly tissue- and stress-specific; the core activity is DNA-binding transcriptional regulation of cell-fate targets. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Tissue specificity / localization of function \| p53 functions predominantly in the nucleus as a transcription factor, but outputs are markedly cell- and tissue-specific.
GO:0005515 protein binding	IPI PMID:20599664 A novel role for cardiac ankyrin repeat protein Ankrd1/CARP ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0008340 determination of adult lifespan	IMP PMID:20818388 Puma is required for p53-induced depletion of adult stem cel...	KEEP AS NON CORE	Summary: determination of adult lifespan is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53. Reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IMP PMID:20818388 Puma is required for p53-induced depletion of adult stem cel...	ACCEPT	Summary: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0070245 positive regulation of thymocyte apoptotic process	IMP PMID:20818388 Puma is required for p53-induced depletion of adult stem cel...	KEEP AS NON CORE	Summary: Positive regulation of thymocyte apoptotic process is a tissue-specific p53 apoptotic output, not the core Trp53 molecular function. Reason: Retain as non-core because thymocyte apoptosis is a cell-type-specific consequence of p53 activation; the core activity is DNA-binding transcriptional regulation of stress-response targets. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Radiosensitive tissues such as thymus, bone marrow, spleen, intestinal epithelium preferentially undergo apoptosis PMID:20818388 p53-dependent apoptosis after DNA damage
GO:0097371 MDM2/MDM4 family protein binding	IPI PMID:20818388 Puma is required for p53-induced depletion of adult stem cel...	KEEP AS NON CORE	Summary: MDM2/MDM4 family protein binding is a valid p53 regulatory interaction, but it belongs outside the core function set. Reason: Retain as non-core because MDM2/MDM4 binding controls p53 stability and activity, whereas the core Trp53 function is sequence-specific transcriptional regulation of stress-response targets. Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. file:mouse/Trp53/Trp53-deep-research-falcon.md MDM4/MDMX restrains p53 transactivation and forms a heterodimer with MDM2 to enhance p53 degradation.
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:19749791 Repression of SHP-1 expression by p53 leads to trkA tyrosine...	ACCEPT	Summary: PMID:19749791 directly supports p53-dependent repression of SHP-1 transcription. Reason: The paper reports endogenous or transfected wild-type p53 repressing SHP-1 expression through the SHP-1 promoter, supporting negative regulation of transcription. Supporting Evidence: PMID:19749791 endogenous wtp53, activated by therapeutic agents, and transfected wtp53 repress expression of SHP-1 PMID:19749791 p53 repression of SHP-1 expression leads to trkA-Y674/Y675 phosphorylation
GO:0008285 negative regulation of cell population proliferation	IMP PMID:19749791 Repression of SHP-1 expression by p53 leads to trkA tyrosine...	ACCEPT	Summary: PMID:19749791 supports p53-dependent suppression of breast-cancer cell proliferation through SHP-1 repression and TrkA activation. Reason: The original evidence directly reports suppressed proliferation when wild-type p53 represses SHP-1 and activates TrkA-dependent signaling. Supporting Evidence: PMID:19749791 show suppressed cell proliferation PMID:19749791 p53 repression of SHP-1 expression leads to trkA-Y674/Y675 phosphorylation and trkA-dependent suppression of breast-cancer cell proliferation.
GO:0045892 negative regulation of DNA-templated transcription	IMP PMID:19749791 Repression of SHP-1 expression by p53 leads to trkA tyrosine...	ACCEPT	Summary: PMID:19749791 directly supports p53-dependent repression of SHP-1 transcription. Reason: The paper reports endogenous or transfected wild-type p53 repressing SHP-1 expression through the SHP-1 promoter, supporting negative regulation of transcription. Supporting Evidence: PMID:19749791 endogenous wtp53, activated by therapeutic agents, and transfected wtp53 repress expression of SHP-1 PMID:19749791 p53 repression of SHP-1 expression leads to trkA-Y674/Y675 phosphorylation
GO:0005515 protein binding	IPI PMID:11672522 Negative control of p53 by Sir2alpha promotes cell survival ...	REMOVE	Summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity. Reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
GO:0003677 DNA binding	ISS GO_REF:0000024	ACCEPT	Summary: DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005507 copper ion binding	ISS GO_REF:0000024	MODIFY	Summary: Copper ion binding is not supported for mouse p53 by the cited evidence; UniProt documents Zn(2+) binding instead. Reason: Replace the unsupported copper-binding term with GO:0008270 zinc ion binding, the metal cofactor documented for p53. Proposed replacements: zinc ion binding Supporting Evidence: file:mouse/Trp53/Trp53-uniprot.txt Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.
GO:0005634 nucleus	ISS GO_REF:0000024	ACCEPT	Summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0005730 nucleolus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: nucleolus is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005737 cytoplasm	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: cytoplasm is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0005739 mitochondrion	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: mitochondrion is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function. Reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence. Supporting Evidence: file:mouse/Trp53/Trp53-deep-research-falcon.md The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
GO:0006289 nucleotide-excision repair	ISS GO_REF:0000024	ACCEPT	Summary: nucleotide-excision repair is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
GO:0030308 negative regulation of cell growth	ISS GO_REF:0000024	ACCEPT	Summary: negative regulation of cell growth is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context. Reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.

Core Functions

Trp53/p53 acts primarily as a nuclear sequence-specific DNA-binding transcription factor that binds p53 response elements and regulates RNA polymerase II target genes controlling DNA damage responses, cell-cycle arrest, apoptosis, and senescence.

Molecular Function:

DNA-binding transcription factor activity, RNA polymerase II-specific

Directly Involved In:

DNA damage response, signal transduction by p53 class mediator positive regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II intrinsic apoptotic signaling pathway by p53 class mediator

Cellular Locations:

nucleus chromatin

Supporting Evidence:

file:mouse/Trp53/Trp53-deep-research-falcon.md
p53 is primarily a sequence-specific DNA-binding transcription factor that regulates stress-responsive gene expression programs.

p53 oligomerization supports DNA binding and transcriptional target selection; the active transcription factor binds DNA as a homotetramer and integrates stress-dependent post-translational regulation with cell fate outputs.

Molecular Function:

RNA polymerase II cis-regulatory region sequence-specific DNA binding

Directly Involved In:

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator positive regulation of cellular senescence

Cellular Locations:

nucleus nucleoplasm

Supporting Evidence:

file:mouse/Trp53/Trp53-uniprot.txt
Forms homodimers and homotetramers. Binds DNA as a homotetramer.
file:mouse/Trp53/Trp53-deep-research-falcon.md
DNA binding is coupled to oligomerization: p53 transitions ... to a functional tetramer.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10329544

Hepatitis C virus core protein interacts with a human DEAD box protein DDX3.

PMID:10562313

A proinflammatory cytokine inhibits p53 tumor suppressor activity.

PMID:11181729

The AKT3 potassium channel protein interacts with the AtPP2CA protein phosphatase 2C.

PMID:11274052

Naked cuticle targets dishevelled to antagonize Wnt signal transduction.

PMID:11672522

Negative control of p53 by Sir2alpha promotes cell survival under stress.

PMID:11781573

Design and application of a cytokine-receptor-based interaction trap.

PMID:12667443

p53 has a direct apoptogenic role at the mitochondria.

PMID:15532030

Coexpression of Brn-3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis.

PMID:16151013

PUMA couples the nuclear and cytoplasmic proapoptotic function of p53.

PMID:16213212

Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin.

PMID:16407291

Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53.

PMID:16480949

The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein.

PMID:16697373

Interaction of nucleoside diphosphate kinase and catalases for stress and light responses in Neurospora crassa.

PMID:17535810

Functional similarity between the chloroplast translocon component, Tic40, and the human co-chaperone, Hsp70-interacting protein (Hip).

PMID:17936560

Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation.

PMID:18025262

Interaction between transcription factor, basal transcription factor 3, and the NH2-terminal domain of human estrogen receptor alpha.

PMID:18303029

BAF60a interacts with p53 to recruit the SWI/SNF complex.

PMID:18359851

Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2.

PMID:18448518

The nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha.

PMID:18695251

AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53.

PMID:19011633

Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin.

PMID:19556538

Trim24 targets endogenous p53 for degradation.

PMID:19749791

Repression of SHP-1 expression by p53 leads to trkA tyrosine phosphorylation and suppression of breast cancer cell proliferation.

PMID:20599664

A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein.

PMID:20621096

Deletion of Swm2p selectively impairs trimethylation of snRNAs by trimethylguanosine synthase (Tgs1p).

PMID:20697359

Regulation of MDM4 (MDMX) function by p76(MDM2): a new facet in the control of p53 activity.

PMID:20708612

DJ-1, an oncogene and causative gene for familial Parkinson's disease, is essential for SV40 transformation in mouse fibroblasts through up-regulation of c-Myc.

PMID:20818388

Puma is required for p53-induced depletion of adult stem cells.

PMID:20832751

An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction.

PMID:21057544

p85α mediates p53 K370 acetylation by p300 and regulates its promoter-specific transactivity in the cellular UVB response.

PMID:21122074

Interaction of Sesbania mosaic virus movement protein with the coat protein--implications for viral spread.

PMID:21670284

Near-UV cyanobacteriochrome signaling system elicits negative phototaxis in the cyanobacterium Synechocystis sp. PCC 6803.

PMID:21741598

A Pin1/mutant p53 axis promotes aggressiveness in breast cancer.

PMID:21857681

A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1.

PMID:21909133

Manganese superoxide dismutase is a mitochondrial fidelity protein that protects Polγ against UV-induced inactivation.

PMID:22056770

Structural basis for the molecular evolution of SRP-GTPase activation by protein.

PMID:22262176

Ribosomal stress induces L11- and p53-dependent apoptosis in mouse pluripotent stem cells.

PMID:22726440

p53 opens the mitochondrial permeability transition pore to trigger necrosis.

PMID:23123091

Involvement of PTEN in TPA-mediated p53-activation in mouse skin epidermal JB6 cells.

PMID:23629966

Deacetylation of p53 induces autophagy by suppressing Bmf expression.

PMID:23980194

E258K HCM-causing mutation in cardiac MyBP-C reduces contractile force and accelerates twitch kinetics by disrupting the cMyBP-C and myosin S2 interaction.

PMID:24051492

p53 regulates Period2 expression and the circadian clock.

PMID:24116158

The nuclear envelope protein, LAP1B, is a novel protein phosphatase 1 substrate.

PMID:24240685

FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage.

PMID:25117711

Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and development, but essential in response to DNA damage.

PMID:26960425

Yeast Two-Hybrid Screening for Proteins that Interact with the Extracellular Domain of Amyloid Precursor Protein.

PMID:27258785

The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873.

PMID:28536627

The identification of human aldo-keto reductase AKR7A2 as a novel cytoglobin-binding partner.

PMID:30089260

p53 Regulates the Expression of LRP1 and Apoptosis through a Stress Intensity-Dependent MicroRNA Feedback Loop.

PMID:37025149

Arabidopsis LFR, a SWI/SNF complex component, interacts with ICE1 and activates ICE1 and CBF3 expression in cold acclimation.

PMID:9194565

Binding and modulation of p53 by p300/CBP coactivators.

Reactome:R-MMU-9816449

Dppa2 and Dppa4 bind the Dux gene cluster

file:mouse/Trp53/Trp53-uniprot.txt

UniProt record for mouse Trp53

Trp53 encodes p53, a multifunctional transcription factor that induces cell cycle arrest, DNA repair, or apoptosis after binding target DNA sequences.

"Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence."

file:mouse/Trp53/Trp53-deep-research-falcon.md

Falcon deep research report on mouse Trp53

Falcon synthesis verifies mouse Trp53/p53 as a sequence-specific DNA-binding transcription factor with tissue- and stress-specific outputs.

"Mouse Tp53 (Trp53; UniProt P02340) encodes p53, a stress-activated, sequence-specific DNA-binding transcription factor."

Suggested Experiments

Experiment: Use Trp53 response-reporter mouse cells with matched DNA damage, hypoxia, and metabolic stress treatments to map direct p53 binding, target transcription, and cell fate outputs by tissue.

Experiment: Compare wild-type and DNA-binding-defective Trp53 alleles in primary mouse cells to separate direct transcriptional effects from non-transcriptional mitochondrial apoptosis functions.

📚 Additional Documentation

Deep Research Bioreason

(Trp53-deep-research-bioreason.md)

BioReason Chat Export

Exported on March 22, 2026 at 01:33 AM

Organism: Mus musculus

Sequence:

MTAMEESQSDISLELPLSQETFSGLWKLLPPEDILPSPHCMDDLLLPQDVEEFFEGPSEALRVSGAPAAQDPVTETPGPVAPAPATPWPLSSFVPSQKTYQGNYGFHLGFLQSGTAKSVMCTYSPPLNKLFCQLAKTCPVQLWVSATPPAGSRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNLYPEYLEDRQTFRHSVVVPYEPPEAGSEYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEVLCPELPPGSAKRALPTCTSASPPQKKKPLDGEYFTLKIRGRKRFEMFRELNEALELKDAHATEESGDSRAHSSYLKTKKGQSTSRHKKTMVKKVGPDSD

Thinking Trace

I begin by dissecting the InterPro architecture. The protein is classified broadly by IPR002117 (p53 tumour suppressor family, residues 6–362), immediately suggesting a transcriptional regulator that orchestrates stress and checkpoint pathways. Near the N-terminus sits IPR013872 (p53, transactivation domain, residues 9–32), a low-complexity activation module that recruits coactivators and corepressors. The central core comprises IPR011615 (p53, DNA-binding domain, residues 97–286), reinforced by two overlapping superfamily signatures—IPR012346 (p53/RUNT-type transcription factor, DNA-binding domain superfamily, residues 92–292) and IPR008967 (p53-like transcription factor, DNA-binding domain superfamily, residues 94–284)—which together define a structured site-recognition fold that binds specific DNA elements and couples sequence-specific contacts to regulatory responses. Embedded within this core is IPR057064 (p53, central conserved site, residues 234–246), a hallmark motif that stabilizes the DNA-binding architecture and coordinates allosteric communication. At the C-terminus, IPR010991 (p53, tetramerisation domain, residues 316–353) and its higher-order envelope IPR036674 (p53-like tetramerisation domain superfamily, residues 316–357) enforce assembly into a homotetramer. This ordered layout—an N-terminal activation region, a central site-specific DNA-binding core with a conserved stabilization motif, and a C-terminal oligomerization hub—causally dictates a sequence-specific DNA-binding transcription factor that operates as a tetrameric switch.

From these domains, the molecular function follows directly. The presence of a dedicated transactivation domain (IPR013872) coupled to the structured DNA-binding core (IPR011615 and its superfamilies) establishes RNA polymerase II-dependent transcriptional regulation. The tetramerisation module (IPR010991/IPR036674) amplifies affinity and specificity by cooperative assembly, a common strategy for high-fidelity transcriptional control. This architecture yields DNA-binding transcription factor activity with sequence specificity and supports both activation and repression depending on cofactor recruitment. Therefore, the molecular function is best captured by GO:0003700 DNA-binding transcription factor activity, sequence-specific DNA binding.

Biological process emerges as a consequence of this regulatory capacity. A p53-family transcriptional hub that binds and modulates promoter/enhancer activity is poised to govern checkpoints and stress responses. The conserved central site and tetrameric assembly ensure robust control over gene networks that halt cell cycle progression and promote repair or apoptosis when genomic integrity is compromised. This causal chain aligns with control of the cell cycle and apoptosis and situates the protein at the heart of stress-responsive transcriptional programs. Accordingly, the most defensible process annotations are GO:0051726 regulation of cell cycle and GO:0006915 apoptotic process.

Cellular location follows from function and architecture. A DNA-binding transcriptional regulator must access chromatin; the presence of a transactivation domain and a canonical DNA-binding core necessitate nuclear residence, consistent with a soluble nuclear regulator. Thus, the cellular component is the nucleus (GO:0005634).

Mechanistically, I hypothesize a tetrameric transcriptional switch that senses intracellular stress and enforces checkpoints. The N-terminal activation domain recruits chromatin-modifying coactivators (e.g., acetyltransferases) or corepressors, while the central domain binds specific promoter elements and transmits signals through the conserved site to tune transcriptional output. The tetramerisation domain concentrates binding interfaces to stabilize higher-order assemblies on DNA. Likely partners include E3 ubiquitin ligases that set protein turnover thresholds, chromatin remodelers that gate promoter accessibility, and checkpoint kinases that phosphorylate and modulate its activity. Together, these interactions allow dynamic repression or activation of genes governing cell cycle arrest and apoptosis within the nucleus.

Functional Summary

A nuclear, tetramer-forming transcriptional regulator that uses an N‑terminal activation module and a central site-recognition core to control RNA polymerase II–dependent gene programs. By assembling into a cooperative homotetramer, it binds specific promoter elements, recruits chromatin-modifying cofactors, and toggles between activation and repression to enforce checkpoint pathways that govern cell cycle control and trigger apoptosis under stress.

UniProt Summary

Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activating protein that acts downstream of a signal mediated by a DNA damage-stress pathway. Appears to regulate at least two distinct pathways: the mediation of apoptotic pathways by p53/TP53, and repression of cell cycle progression by impeding the G2/M transition (By similarity).

InterPro Domains

p53 tumour suppressor family (IPR002117, family) — residues 6-362
p53, transactivation domain (IPR013872, domain) — residues 9-32
p53/RUNT-type transcription factor, DNA-binding domain superfamily (IPR012346, homologous_superfamily) — residues 92-292
p53-like transcription factor, DNA-binding domain superfamily (IPR008967, homologous_superfamily) — residues 94-284
p53, DNA-binding domain (IPR011615, domain) — residues 97-286
p53, central conserved site (IPR057064, conserved_site) — residues 234-246
p53, tetramerisation domain (IPR010991, domain) — residues 316-353
p53-like tetramerisation domain superfamily (IPR036674, homologous_superfamily) — residues 316-357

GO Terms

Molecular Function: molecular_function (GO:0003674), molecular function regulator activity (GO:0098772), binding (GO:0005488), transcription regulator activity (GO:0140110), enzyme regulator activity (GO:0030234), DNA-binding transcription factor activity, sequence-specific DNA binding (GO:0003700), organic cyclic compound binding (GO:0097159), heterocyclic compound binding (GO:1901363), chromatin binding (GO:0003682), protein binding (GO:0005515), nucleic acid binding (GO:0003676), DNA-binding transcription activator activity (GO:0001216), enzyme binding (GO:0019899), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), ubiquitin-like protein ligase binding (GO:0044389), transcription regulatory region nucleic acid binding (GO:0001067), DNA binding (GO:0003677), ubiquitin protein ligase binding (GO:0031625), sequence-specific DNA binding (GO:0043565), transcription cis-regulatory region binding (GO:0000976), double-stranded DNA binding (GO:0003690), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)

Biological Process: biological_process (GO:0008150), localization (GO:0051179), signaling (GO:0023052), biological regulation (GO:0065007), response to stimulus (GO:0050896), biological process involved in interspecies interaction between organisms (GO:0044419), growth (GO:0040007), negative regulation of biological process (GO:0048519), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), multicellular organismal process (GO:0032501), rhythmic process (GO:0048511), developmental process (GO:0032502), cellular process (GO:0009987), metabolic process (GO:0008152), immune system process (GO:0002376), cellular localization (GO:0051641), anatomical structure development (GO:0048856), negative regulation of signaling (GO:0023057), immune response (GO:0006955), cell cycle process (GO:0022402), pattern specification process (GO:0007389), cellular component organization or biogenesis (GO:0071840), regulation of multicellular organismal process (GO:0051239), anatomical structure formation involved in morphogenesis (GO:0048646), negative regulation of metabolic process (GO:0009892), regulation of biological quality (GO:0065008), regulation of cellular process (GO:0050794), regulation of response to stimulus (GO:0048583), cellular response to stimulus (GO:0051716), multicellular organism growth (GO:0035264), process utilizing autophagic mechanism (GO:0061919), negative regulation of cellular process (GO:0048523), cellular developmental process (GO:0048869), response to abiotic stimulus (GO:0009628), biosynthetic process (GO:0009058), regulation of metabolic process (GO:0019222), establishment of localization (GO:0051234), catabolic process (GO:0009056), macromolecule localization (GO:0033036), negative regulation of gene silencing by RNA (GO:0060967), immune effector process (GO:0002252), negative regulation of post-transcriptional gene silencing (GO:0060149), cell communication (GO:0007154), positive regulation of cellular process (GO:0048522), response to external stimulus (GO:0009605), developmental growth (GO:0048589), anatomical structure morphogenesis (GO:0009653), response to chemical (GO:0042221), leukocyte activation (GO:0045321), cell population proliferation (GO:0008283), nitrogen compound metabolic process (GO:0006807), negative regulation of multicellular organismal process (GO:0051241), regulation of developmental process (GO:0050793), response to biotic stimulus (GO:0009607), cell death (GO:0008219), response to endogenous stimulus (GO:0009719), regulation of signaling (GO:0023051), negative regulation of developmental process (GO:0051093), response to other organism (GO:0051707), signal transduction (GO:0007165), multicellular organism development (GO:0007275), cell activation (GO:0001775), determination of adult lifespan (GO:0008340), regulation of circadian rhythm (GO:0042752), circadian rhythm (GO:0007623), cell cycle (GO:0007049), organic substance metabolic process (GO:0071704), cellular metabolic process (GO:0044237), small molecule metabolic process (GO:0044281), positive regulation of metabolic process (GO:0009893), response to stress (GO:0006950), negative regulation of response to stimulus (GO:0048585), primary metabolic process (GO:0044238), behavior (GO:0007610), negative regulation of post-transcriptional gene silencing by RNA (GO:1900369), neural precursor cell proliferation (GO:0061351), negative regulation of cellular component organization (GO:0051129), response to external biotic stimulus (GO:0043207), reactive oxygen species metabolic process (GO:0072593), response to radiation (GO:0009314), regulation of response to stress (GO:0080134), stem cell proliferation (GO:0072089), regulation of tissue remodeling (GO:0034103), animal organ development (GO:0048513), regulation of signal transduction (GO:0009966), regulation of macromolecule metabolic process (GO:0060255), cellular aromatic compound metabolic process (GO:0006725), carbohydrate metabolic process (GO:0005975), negative regulation of cell cycle process (GO:0010948), establishment of protein localization (GO:0045184), autophagy (GO:0006914), response to inorganic substance (GO:0010035), intracellular transport (GO:0046907), cardiac septum morphogenesis (GO:0060411), negative regulation of macromolecule metabolic process (GO:0010605), organic acid metabolic process (GO:0006082), embryo development (GO:0009790), negative regulation of cell cycle (GO:0045786), cellular macromolecule metabolic process (GO:0044260), regulation of cell cycle process (GO:0010564), positive regulation of nitrogen compound metabolic process (GO:0051173), regulation of membrane permeability (GO:0090559), negative regulation of nitrogen compound metabolic process (GO:0051172), organic substance biosynthetic process (GO:1901576), small molecule catabolic process (GO:0044282), positive regulation of macromolecule metabolic process (GO:0010604), heterocycle metabolic process (GO:0046483), negative regulation of cell population proliferation (GO:0008285), regulation of cellular response to stress (GO:0080135), glial cell proliferation (GO:0014009), hindbrain development (GO:0030902), establishment of localization in cell (GO:0051649), cellular biosynthetic process (GO:0044249), monosaccharide metabolic process (GO:0005996), cellular nitrogen compound metabolic process (GO:0034641), regulation of protein stability (GO:0031647), macromolecule metabolic process (GO:0043170), positive regulation of biosynthetic process (GO:0009891), negative regulation of carbohydrate metabolic process (GO:0045912), innate immune response (GO:0045087), defense response to other organism (GO:0098542), regulation of multicellular organismal development (GO:2000026), cellular response to environmental stimulus (GO:0104004), regulation of cell population proliferation (GO:0042127), regulation of cell death (GO:0010941), somitogenesis (GO:0001756), regionalization (GO:0003002), positive regulation of cellular metabolic process (GO:0031325), cellular response to stress (GO:0033554), negative regulation of cell differentiation (GO:0045596), transport (GO:0006810), cellular macromolecule localization (GO:0070727), regulation of cellular metabolic process (GO:0031323), negative regulation of catabolic process (GO:0009895), negative regulation of biosynthetic process (GO:0009890), regulation of primary metabolic process (GO:0080090), generation of precursor metabolites and energy (GO:0006091), rhythmic behavior (GO:0007622), regulation of cellular response to growth factor stimulus (GO:0090287), negative regulation of signal transduction (GO:0009968), positive regulation of cell death (GO:0010942), response to hypoxia (GO:0001666), programmed cell death (GO:0012501), negative regulation of cell death (GO:0060548), cell development (GO:0048468), leukocyte activation involved in immune response (GO:0002366), response to xenobiotic stimulus (GO:0009410), cell differentiation (GO:0030154), negative regulation of nervous system development (GO:0051961), cellular catabolic process (GO:0044248), system development (GO:0048731), response to oxygen levels (GO:0070482), cardiac septum development (GO:0003279), response to growth factor (GO:0070848), cellular response to endogenous stimulus (GO:0071495), lymphocyte activation (GO:0046649), neuron death (GO:0070997), regulation of cell cycle (GO:0051726), regulation of catabolic process (GO:0009894), cerebellum development (GO:0021549), animal organ morphogenesis (GO:0009887), organic cyclic compound metabolic process (GO:1901360), leukocyte proliferation (GO:0070661), cellular response to abiotic stimulus (GO:0071214), apoptotic signaling pathway (GO:0097190), regulation of nitrogen compound metabolic process (GO:0051171), negative regulation of small molecule metabolic process (GO:0062014), regulation of cell differentiation (GO:0045595), cellular component organization (GO:0016043), cell surface receptor signaling pathway (GO:0007166), organic substance catabolic process (GO:1901575), regulation of cellular component organization (GO:0051128), organic hydroxy compound metabolic process (GO:1901615), negative regulation of cell communication (GO:0010648), mitotic cell cycle process (GO:1903047), intracellular signal transduction (GO:0035556), response to oxidative stress (GO:0006979), defense response (GO:0006952), response to osmotic stress (GO:0006970), circadian behavior (GO:0048512), cardiac chamber development (GO:0003205), negative regulation of cellular metabolic process (GO:0031324), metencephalon development (GO:0022037), response to organic substance (GO:0010033), necrotic cell death (GO:0070265), fibroblast proliferation (GO:0048144), cell fate commitment (GO:0045165), embryonic morphogenesis (GO:0048598), nucleobase-containing compound metabolic process (GO:0006139), head development (GO:0060322), regulation of cell communication (GO:0010646), tissue development (GO:0009888), cellular response to chemical stimulus (GO:0070887), cell activation involved in immune response (GO:0002263), regulation of biosynthetic process (GO:0009889), regulation of small molecule metabolic process (GO:0062012), entrainment of circadian clock (GO:0009649), cardiac chamber morphogenesis (GO:0003206), response to ischemia (GO:0002931), mitotic cell cycle (GO:0000278), nitrogen compound transport (GO:0071705), monosaccharide catabolic process (GO:0046365), T cell lineage commitment (GO:0002360), regulation of macromolecule biosynthetic process (GO:0010556), cellular response to oxygen levels (GO:0071453), regulation of protein metabolic process (GO:0051246), oxoacid metabolic process (GO:0043436), negative regulation of neural precursor cell proliferation (GO:2000178), negative regulation of reactive oxygen species metabolic process (GO:2000378), regulation of cellular carbohydrate metabolic process (GO:0010675), positive regulation of necrotic cell death (GO:0010940), regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090092), regulation of glial cell proliferation (GO:0060251), organic substance transport (GO:0071702), mitotic cell cycle checkpoint signaling (GO:0007093), regulation of gene expression (GO:0010468), entrainment of circadian clock by photoperiod (GO:0043153), regulation of neural precursor cell proliferation (GO:2000177), positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus (GO:1901522), intracellular protein transport (GO:0006886), negative regulation of autophagy (GO:0010507), circulatory system development (GO:0072359), response to decreased oxygen levels (GO:0036293), regulation of DNA-templated transcription in response to stress (GO:0043620), negative regulation of mitotic cell cycle (GO:0045930), intrinsic apoptotic signaling pathway (GO:0097193), negative regulation of fibroblast proliferation (GO:0048147), energy derivation by oxidation of organic compounds (GO:0015980), carbohydrate catabolic process (GO:0016052), cytokine-mediated signaling pathway (GO:0019221), cellular component disassembly (GO:0022411), negative regulation of gene expression (GO:0010629), B cell activation (GO:0042113), heart development (GO:0007507), mitochondrial transport (GO:0006839), positive regulation of neuron death (GO:1901216), cellular response to radiation (GO:0071478), cellular response to hypoxia (GO:0071456), response to transforming growth factor beta (GO:0071559), response to light stimulus (GO:0009416), hexose metabolic process (GO:0019318), lymphocyte proliferation (GO:0046651), leukocyte differentiation (GO:0002521), enzyme-linked receptor protein signaling pathway (GO:0007167), regulation of reactive oxygen species metabolic process (GO:2000377), regulation of DNA metabolic process (GO:0051052), cellular response to DNA damage stimulus (GO:0006974), cellular response to organic substance (GO:0071310), signal transduction in response to DNA damage (GO:0042770), aromatic compound biosynthetic process (GO:0019438), establishment of protein localization to organelle (GO:0072594), regulation of cell development (GO:0060284), negative regulation of protein metabolic process (GO:0051248), regulation of glucose metabolic process (GO:0010906), regulation of autophagy (GO:0010506), regulation of neuron death (GO:1901214), response to salt stress (GO:0009651), regulation of response to DNA damage stimulus (GO:2001020), macroautophagy (GO:0016236), response to endoplasmic reticulum stress (GO:0034976), positive regulation of macromolecule biosynthetic process (GO:0010557), neurogenesis (GO:0022008), negative regulation of organelle organization (GO:0010639), regulation of generation of precursor metabolites and energy (GO:0043467), positive regulation of RNA metabolic process (GO:0051254), neuron apoptotic process (GO:0051402), apoptotic process (GO:0006915), regulation of cellular biosynthetic process (GO:0031326), regulation of stem cell proliferation (GO:0072091), regulation of nucleobase-containing compound metabolic process (GO:0019219), regulation of organelle organization (GO:0033043), cellular nitrogen compound biosynthetic process (GO:0044271), protein localization (GO:0008104), regulation of cellular response to transforming growth factor beta stimulus (GO:1903844), epithelium development (GO:0060429), negative regulation of cell development (GO:0010721), positive regulation of cellular biosynthetic process (GO:0031328), lymphocyte activation involved in immune response (GO:0002285), cellular response to growth factor stimulus (GO:0071363), embryo development ending in birth or egg hatching (GO:0009792), negative regulation of cell cycle phase transition (GO:1901988), macromolecule biosynthetic process (GO:0009059), organic cyclic compound biosynthetic process (GO:1901362), regulation of mitotic cell cycle (GO:0007346), regulation of cellular senescence (GO:2000772), regulation of fibroblast proliferation (GO:0048145), negative regulation of programmed cell death (GO:0043069), regulation of programmed cell death (GO:0043067), negative regulation of cellular catabolic process (GO:0031330), gastrulation (GO:0007369), nuclear transport (GO:0051169), signal transduction by p53 class mediator (GO:0072331), lymphocyte differentiation (GO:0030098), brain development (GO:0007420), negative regulation of neurogenesis (GO:0050768), embryonic organ development (GO:0048568), negative regulation of DNA metabolic process (GO:0051053), nervous system development (GO:0007399), heart morphogenesis (GO:0003007), nucleic acid metabolic process (GO:0090304), protein transport (GO:0015031), heterocycle biosynthetic process (GO:0018130), DNA metabolic process (GO:0006259), central nervous system development (GO:0007417), negative regulation of glial cell proliferation (GO:0060253), negative regulation of cellular biosynthetic process (GO:0031327), regulation of RNA metabolic process (GO:0051252), response to ionizing radiation (GO:0010212), release of cytochrome c from mitochondria (GO:0001836), gene expression (GO:0010467), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), negative regulation of stem cell proliferation (GO:2000647), programmed necrotic cell death (GO:0097300), membrane organization (GO:0061024), neuroblast proliferation (GO:0007405), hemopoiesis (GO:0030097), response to cytokine (GO:0034097), segmentation (GO:0035282), regulation of carbohydrate catabolic process (GO:0043470), cell cycle checkpoint signaling (GO:0000075), positive regulation of phosphorus metabolic process (GO:0010562), negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090101), positive regulation of programmed cell death (GO:0043068), positive regulation of membrane permeability (GO:1905710), autophagy of mitochondrion (GO:0000422), lactate metabolic process (GO:0006089), positive regulation of gene expression (GO:0010628), regulation of carbohydrate metabolic process (GO:0006109), regulation of nervous system development (GO:0051960), regulation of apoptotic signaling pathway (GO:2001233), somite development (GO:0061053), mononuclear cell proliferation (GO:0032943), regulation of necrotic cell death (GO:0010939), nucleobase-containing compound biosynthetic process (GO:0034654), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), regulation of mitochondrial membrane permeability (GO:0046902), negative regulation of miRNA-mediated gene silencing (GO:0060965), regulation of cell cycle phase transition (GO:1901987), positive regulation of protein metabolic process (GO:0051247), T cell activation (GO:0042110), negative regulation of macromolecule biosynthetic process (GO:0010558), protein stabilization (GO:0050821), response to type II interferon (GO:0034341), regulation of cellular catabolic process (GO:0031329), organelle organization (GO:0006996), negative regulation of RNA metabolic process (GO:0051253), regulation of intracellular signal transduction (GO:1902531), regulation of phosphorus metabolic process (GO:0051174), anterior/posterior pattern specification (GO:0009952), glucose metabolic process (GO:0006006), photoperiodism (GO:0009648), mitochondrion organization (GO:0007005), selective autophagy (GO:0061912), RNA metabolic process (GO:0016070), regulation of apoptotic process (GO:0042981), negative regulation of gliogenesis (GO:0014014), positive regulation of phosphate metabolic process (GO:0045937), regulation of RNA biosynthetic process (GO:2001141), regulation of neuron apoptotic process (GO:0043523), DNA repair (GO:0006281), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), cellular response to cytokine stimulus (GO:0071345), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), mitotic DNA integrity checkpoint signaling (GO:0044774), regulation of DNA replication (GO:0006275), positive regulation of RNA biosynthetic process (GO:1902680), regulation of transcription from RNA polymerase II promoter in response to stress (GO:0043618), positive regulation of protein modification process (GO:0031401), regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902108), nucleocytoplasmic transport (GO:0006913), cellular response to transforming growth factor beta stimulus (GO:0071560), positive regulation of apoptotic process (GO:0043065), regulation of intrinsic apoptotic signaling pathway (GO:2001242), regulation of gene silencing by RNA (GO:0060966), hexose catabolic process (GO:0019320), regulation of signal transduction by p53 class mediator (GO:1901796), necroptotic process (GO:0070266), cellular response to ionizing radiation (GO:0071479), response to gamma radiation (GO:0010332), fermentation (GO:0006113), cellular response to light stimulus (GO:0071482), gliogenesis (GO:0042063), regulation of programmed necrotic cell death (GO:0062098), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), negative regulation of cell cycle G1/S phase transition (GO:1902807), negative regulation of proteolysis (GO:0045861), response to X-ray (GO:0010165), RNA biosynthetic process (GO:0032774), nucleic acid-templated transcription (GO:0097659), negative regulation of mitochondrion organization (GO:0010823), protein import into nucleus (GO:0006606), T cell activation involved in immune response (GO:0002286), mitochondrial DNA metabolic process (GO:0032042), regulation of proteolysis (GO:0030162), regulation of production of small RNA involved in gene silencing by RNA (GO:0070920), regulation of mitochondrion organization (GO:0010821), muscle cell apoptotic process (GO:0010657), apoptotic mitochondrial changes (GO:0008637), carboxylic acid metabolic process (GO:0019752), T cell proliferation (GO:0042098), transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0007178), mitochondrial membrane organization (GO:0007006), negative regulation of macroautophagy (GO:0016242), interferon-mediated signaling pathway (GO:0140888), mitophagy (GO:0000423), mononuclear cell differentiation (GO:1903131), response to UV (GO:0009411), regulation of neuroblast proliferation (GO:1902692), regulation of neurogenesis (GO:0050767), generation of neurons (GO:0048699), regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043516), negative regulation of RNA biosynthetic process (GO:1902679), DNA damage checkpoint signaling (GO:0000077), regulation of post-transcriptional gene silencing (GO:0060147), negative regulation of DNA replication (GO:0008156), positive regulation of neuron apoptotic process (GO:0043525), DNA integrity checkpoint signaling (GO:0031570), chordate embryonic development (GO:0043009), protein localization to organelle (GO:0033365), DNA damage response, signal transduction by p53 class mediator (GO:0030330), regulation of protein modification process (GO:0031399), T cell differentiation (GO:0030217), negative regulation of mitotic cell cycle phase transition (GO:1901991), regulation of macroautophagy (GO:0016241), negative regulation of neuroblast proliferation (GO:0007406), negative regulation of apoptotic process (GO:0043066), regulation of DNA-templated transcription (GO:0006355), chromosome organization (GO:0051276), organelle disassembly (GO:1903008), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), regulation of phosphate metabolic process (GO:0019220), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), positive regulation of mitochondrial membrane permeability (GO:0035794), cellular response to decreased oxygen levels (GO:0036294), positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress (GO:1990440), regulation of mitotic cell cycle phase transition (GO:1901990), mitotic G1/S transition checkpoint signaling (GO:0044819), regulation of autophagy of mitochondrion (GO:1903146), B cell differentiation (GO:0030183), leukocyte apoptotic process (GO:0071887), regulation of cell cycle G1/S phase transition (GO:1902806), cellular response to type II interferon (GO:0071346), in utero embryonic development (GO:0001701), positive regulation of transcription from RNA polymerase II promoter in response to stress (GO:0036003), regulation of leukocyte apoptotic process (GO:2000106), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), mitotic G1 DNA damage checkpoint signaling (GO:0031571), regulation of muscle cell apoptotic process (GO:0010660), regulation of fibroblast apoptotic process (GO:2000269), positive regulation of leukocyte apoptotic process (GO:2000108), positive regulation of nucleic acid-templated transcription (GO:1903508), regulation of post-transcriptional gene silencing by RNA (GO:1900368), positive regulation of phosphorylation (GO:0042327), glucose catabolic process (GO:0006007), positive regulation of protein phosphorylation (GO:0001934), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), double-strand break repair (GO:0006302), regulation of transcription by RNA polymerase II (GO:0006357), mitotic DNA damage checkpoint signaling (GO:0044773), regulation of miRNA maturation (GO:1903798), positive regulation of DNA-templated transcription (GO:0045893), regulation of histone modification (GO:0031056), regulation of intrinsic apoptotic signaling pathway by p53 class mediator (GO:1902253), T cell differentiation in thymus (GO:0033077), type II interferon-mediated signaling pathway (GO:0060333), response to UV-C (GO:0010225), cellular response to UV (GO:0034644), mitochondrial genome maintenance (GO:0000002), protein localization to nucleus (GO:0034504), positive regulation of histone modification (GO:0031058), import into nucleus (GO:0051170), regulation of protein phosphorylation (GO:0001932), negative regulation of DNA-templated transcription (GO:0045892), lymphocyte apoptotic process (GO:0070227), monocarboxylic acid metabolic process (GO:0032787), regulation of nucleic acid-templated transcription (GO:1903506), regulation of protein deacetylation (GO:0090311), DNA-templated transcription (GO:0006351), regulation of mitophagy (GO:1901524), ncRNA metabolic process (GO:0034660), regulation of phosphorylation (GO:0042325), mitochondrion disassembly (GO:0061726), positive regulation of protein deacetylation (GO:0090312), DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest (GO:0006977), regulation of gliogenesis (GO:0014013), positive regulation of muscle cell apoptotic process (GO:0010661), negative regulation of nucleic acid-templated transcription (GO:1903507), regulation of G1/S transition of mitotic cell cycle (GO:2000045), transforming growth factor beta receptor signaling pathway (GO:0007179), cellular response to gamma radiation (GO:0071480), glycolytic fermentation (GO:0019660), ncRNA transcription (GO:0098781), regulation of lymphocyte apoptotic process (GO:0070228), negative regulation of transcription by RNA polymerase II (GO:0000122), rRNA metabolic process (GO:0016072), regulation of striated muscle cell apoptotic process (GO:0010662), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), regulation of miRNA-mediated gene silencing (GO:0060964), positive regulation of transcription by RNA polymerase II (GO:0045944)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), cytosol (GO:0005829), site of DNA damage (GO:0090734), cytoplasm (GO:0005737), membrane-enclosed lumen (GO:0031974), replication fork (GO:0005657), mitochondrion (GO:0005739), organelle lumen (GO:0043233), site of double-strand break (GO:0035861), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), non-membrane-bounded organelle (GO:0043228), intracellular membrane-bounded organelle (GO:0043231), mitochondrial matrix (GO:0005759), intracellular organelle lumen (GO:0070013), intracellular non-membrane-bounded organelle (GO:0043232), chromosome (GO:0005694), nucleus (GO:0005634), germ cell nucleus (GO:0043073)

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Deep Research Bioreason Rl

(Trp53-deep-research-bioreason-rl.md)

BioReason Chat Export

Exported on March 22, 2026 at 01:33 AM

Organism: Mus musculus

Sequence:

MTAMEESQSDISLELPLSQETFSGLWKLLPPEDILPSPHCMDDLLLPQDVEEFFEGPSEALRVSGAPAAQDPVTETPGPVAPAPATPWPLSSFVPSQKTYQGNYGFHLGFLQSGTAKSVMCTYSPPLNKLFCQLAKTCPVQLWVSATPPAGSRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNLYPEYLEDRQTFRHSVVVPYEPPEAGSEYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEVLCPELPPGSAKRALPTCTSASPPQKKKPLDGEYFTLKIRGRKRFEMFRELNEALELKDAHATEESGDSRAHSSYLKTKKGQSTSRHKKTMVKKVGPDSD

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

p53 tumour suppressor family (IPR002117, family) — residues 6-362
p53, transactivation domain (IPR013872, domain) — residues 9-32
p53/RUNT-type transcription factor, DNA-binding domain superfamily (IPR012346, homologous_superfamily) — residues 92-292
p53-like transcription factor, DNA-binding domain superfamily (IPR008967, homologous_superfamily) — residues 94-284
p53, DNA-binding domain (IPR011615, domain) — residues 97-286
p53, central conserved site (IPR057064, conserved_site) — residues 234-246
p53, tetramerisation domain (IPR010991, domain) — residues 316-353
p53-like tetramerisation domain superfamily (IPR036674, homologous_superfamily) — residues 316-357

GO Terms

Generated by BioReason

Deep Research Falcon

(Trp53-deep-research-falcon.md)

provider: falcon
model: Edison Scientific Literature
cached: false
start_time: '2026-05-03T12:54:50.232493'
end_time: '2026-05-03T13:03:19.105108'
duration_seconds: 508.87
template_file: templates/gene_research_go_focused.md
template_variables:
organism: mouse
gene_id: Trp53
gene_symbol: Tp53
uniprot_accession: P02340
protein_description: 'RecName: Full=Cellular tumor antigen p53; AltName: Full=Tumor
suppressor p53;'
gene_info: Name=Tp53; Synonyms=P53, Trp53;
organism_full: Mus musculus (Mouse).
protein_family: Belongs to the p53 family. .
protein_domains: p53-like_TF_DNA-bd_sf. (IPR008967); p53/RUNT-type_TF_DNA-bd_sf.
(IPR012346); P53_central_site. (IPR057064); p53_DNA-bd. (IPR011615); p53_tetramer_sf.
(IPR036674)
provider_config:
timeout: 600
max_retries: 3
parameters:
allowed_domains: []
temperature: 0.1
citation_count: 23

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P02340
Protein Description: RecName: Full=Cellular tumor antigen p53; AltName: Full=Tumor suppressor p53;
Gene Information: Name=Tp53; Synonyms=P53, Trp53;
Organism (full): Mus musculus (Mouse).
Protein Family: Belongs to the p53 family. .
Key Domains: p53-like_TF_DNA-bd_sf. (IPR008967); p53/RUNT-type_TF_DNA-bd_sf. (IPR012346); P53_central_site. (IPR057064); p53_DNA-bd. (IPR011615); p53_tetramer_sf. (IPR036674)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Tp53" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Tp53' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene Tp53 (gene ID: Trp53, UniProt: P02340) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P02340
Protein Description: RecName: Full=Cellular tumor antigen p53; AltName: Full=Tumor suppressor p53;
Gene Information: Name=Tp53; Synonyms=P53, Trp53;
Organism (full): Mus musculus (Mouse).
Protein Family: Belongs to the p53 family. .
Key Domains: p53-like_TF_DNA-bd_sf. (IPR008967); p53/RUNT-type_TF_DNA-bd_sf. (IPR012346); P53_central_site. (IPR057064); p53_DNA-bd. (IPR011615); p53_tetramer_sf. (IPR036674)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Tp53" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene Tp53 (gene ID: Trp53, UniProt: P02340) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Comprehensive Functional Annotation Report: Mouse Tp53 / Trp53 (UniProt P02340)

0) Target verification (critical disambiguation)

The requested UniProt accession P02340 corresponds to cellular tumor antigen p53 (tumor suppressor p53) encoded by Tp53/Trp53 in Mus musculus (mouse), a member of the p53 family of transcription factors. Recent mouse-focused literature explicitly uses TRP53 for mouse and distinguishes it from human TP53, matching the provided UniProt identity context. (pant2023tissuespecificityand pages 1-2, lieschke2024mousemodelsto pages 1-2)

1) Key concepts and definitions (current understanding)

1.1 Core molecular function

p53 is primarily a sequence-specific DNA-binding transcription factor that regulates stress-responsive gene expression programs to preserve cellular integrity. (liu2024understandingthecomplexity pages 1-3, hassin2023druggingp53in pages 1-2)

A widely cited p53 response element is composed of two decameric half-sites with the general consensus 5′-RRRCWWGYYY-3′ (R = A/G; W = A/T; Y = C/T), separated by 0–13 base pairs. (pant2023tissuespecificityand pages 1-2)

DNA binding is coupled to oligomerization: p53 transitions from mixed monomer/dimer/tetramer states in unstressed cells to a functional tetramer (dimer of dimers) during stress to bind response elements and drive transcription. (liu2024understandingthecomplexity pages 1-3, pant2023tissuespecificityand pages 1-2)

Scale of transcriptional control: a recent high-authority synthesis reports >300 direct target genes, with indirect targets expanding to “several thousands” (including non-coding RNAs). (liu2024understandingthecomplexity pages 3-4)

1.2 Domain architecture (structure-function definitions)

Full-length p53 is organized into five canonical regions:
- N-terminal transactivation domain (TAD; includes TAD1/TAD2)
- Proline-rich domain (PRD)
- Central DNA-binding domain (DBD)
- Tetramerization domain (TD)
- C-terminal regulatory domain (CTD) (liu2024understandingthecomplexity pages 1-3)

In a mouse-centered review, these domains are given residue ranges (human numbering): TAD (1–61), PRD (61–92), DBD (94–292), TD (326–353), and CTD (353–390). (pant2023tissuespecificityand pages 1-2)

A key mechanistic point is that TAD and CTD are intrinsically disordered, enabling cofactor binding and extensive post-translational modification (PTM), while the DBD is well-folded. (liu2024understandingthecomplexity pages 1-3)

1.3 Canonical pathway logic (definitions)

In unstressed cells, p53 is restrained by a negative-feedback architecture:
- MDM2 is a major negative regulator: it ubiquitinates p53 to maintain low basal levels and can export nuclear p53 to the cytoplasm. (liu2024understandingthecomplexity pages 3-4)
- MDM4/MDMX restrains p53 transactivation and forms a heterodimer with MDM2 to enhance p53 degradation. (liu2024understandingthecomplexity pages 3-4, hassin2023druggingp53in pages 1-2)
- ARF (p14ARF in human; functionally analogous axis in mouse) stabilizes p53 by inhibiting/sequestering MDM2 (often described as nucleolar sequestration of MDM2). (zhou2023expandingrolesof pages 1-2)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 Tissue specificity and “spatiotemporal” p53 programs in vivo (2023)

A 2023 review focusing on mouse physiology emphasizes that while p53 regulates “hundreds of genes,” most downstream targets are tissue-specific, and the in vivo p53 transcriptional program remains incompletely mapped. (pant2023tissuespecificityand pages 1-2)

That review provides a systems view of physiological stressors (e.g., UV/DNA damage, ribosomal dysfunction, hypoxia, inflammation, nutrient deprivation) that stabilize p53 and trigger transcriptional programs, and presents a “universal p53 signature” concept alongside tissue-specific targets (visual summary). (pant2023tissuespecificityand media 74b6a444)

2.2 Multi-layer regulation and PTM-centric models of p53 control (2024)

A 2024 Cancer Cell synthesis frames PTMs as central regulators of p53, listing diverse PTMs (ubiquitination, phosphorylation, acetylation, methylation, SUMOylation, NEDDylation, O-GlcNAcylation, ADP-ribosylation, UFMylation, etc.) that together control p53 stability, localization, cofactor recruitment, and target selectivity. (liu2024understandingthecomplexity pages 3-4)

Within this PTM framework:
- Phosphorylation at sites such as S15/T18/S20 can disrupt MDM2 binding and promote transcriptional activation; S46 phosphorylation is linked to stronger apoptotic outputs under severe damage. (liu2024understandingthecomplexity pages 3-4)
- Acetylation of lysines in the DBD is described as critical for promoter-specific activation of programs including cell-cycle arrest, apoptosis, senescence, ferroptosis, and mTOR inhibition, with strong support from knock-in mouse models (see §5). (liu2024understandingthecomplexity pages 3-4)

2.3 New mouse tools enabling in situ p53 cell-fate tracking (2024)

A 2024 EMBO Journal resource introduced:
- Triple-FLAG-tagged Trp53 knock-in mice (for p53 pulldown)
- p53 response reporter mice with fluorescent knock-ins at Puma/Bbc3 and p21/Cdkn1a, enabling cell-level visualization of p53-dependent apoptosis vs arrest/senescence programs in vitro and in vivo. (lieschke2024mousemodelsto pages 1-2)

This paper highlights that p53 binds as a homo-tetramer to a consensus motif in regulatory regions of approximately ~500 direct target genes, and that Puma and p21 represent canonical branches toward apoptosis and arrest/senescence, respectively. (lieschke2024mousemodelsto pages 1-2)

3) Functional annotation: biological processes, pathways, and cellular localization

3.1 Subcellular localization (where p53 acts)

Functionally, p53 acts predominantly in the nucleus as a transcription factor. Consistent with this, MDM2-mediated regulation explicitly includes export of nuclear p53 to the cytoplasm, and stress-dependent disruption of this repression allows nuclear accumulation and transcriptional activation. (liu2024understandingthecomplexity pages 3-4, pant2023tissuespecificityand pages 2-3)

3.2 Canonical stress→p53→cell fate pathways

Mouse-focused reviews emphasize that p53 is stabilized and activated by diverse intrinsic and extrinsic stressors including DNA damage, hypoxia, metabolic dysfunction, perturbations to ribosomal biogenesis, nutrient deprivation, and inflammation. (pant2023tissuespecificityand pages 2-3, pant2023tissuespecificityand media 74b6a444)

Canonical effector branches in vivo include:
- Cell-cycle arrest / senescence, prominently via Cdkn1a (p21). (pant2023tissuespecificityand pages 3-4, lieschke2024mousemodelsto pages 1-2)
- Apoptosis, prominently via Bbc3 (Puma); Puma is presented as a key p53 target gene used experimentally as an apoptosis reporter in vivo. (pant2023tissuespecificityand pages 3-4, lieschke2024mousemodelsto pages 1-2)

A pathway-level review also lists additional p53 target genes in arrest and apoptosis modules (e.g., 14-3-3σ, GADD45, Reprimo for arrest; Bax, Noxa, Apaf1 for intrinsic apoptosis), and connects p53 to signaling nodes such as AMPK/TSC2/mTORC1 and PTEN/PI3K regulation. (zhou2023expandingrolesof pages 10-12)

3.3 Metabolism and ferroptosis (expanding functional scope)

The 2023 mouse review describes p53 as responsive to nutrient availability: inhibition of AKT–mTOR and activation of AMPK induce p53, which then upregulates oxidative phosphorylation genes such as GLS2 and SCO2, while decreasing glucose importers GLUT1 and GLUT4 to oppose glycolysis. (pant2023tissuespecificityand pages 2-3)

A 2024 high-authority synthesis expands p53’s tumor-suppressive mechanisms to include metabolism and ferroptosis, describing ferroptosis as an iron-dependent death program modulated by p53 targets including SLC7A11, VKORC1L1, GLS2, and PLTP; this framework is linked to mouse genetics via acetylation-defective knock-ins (next section). (liu2024understandingthecomplexity pages 6-8)

4) Expert opinions and authoritative analysis (what leading reviews emphasize)

4.1 p53 as “undruggable” but increasingly actionable

A 2023 Nature Reviews Drug Discovery review emphasizes that p53 is hard to target pharmacologically because it is a nuclear transcription factor without classic drug-target features, and notes that no p53-based therapeutics had been approved in the US/EU at the time of publication. (hassin2023druggingp53in pages 1-2)

Nevertheless, that review argues the field is advancing through multiple strategies, including:
- Small molecules that protect wild-type p53 from negative regulators (e.g., MDM2/MDM4 axis)
- Compounds that restore mutant p53 function
- Renewed interest in gene therapy and p53-based immunotherapy (hassin2023druggingp53in pages 1-2, hassin2023druggingp53in pages 2-3)

4.2 Context-dependence is central to interpreting p53 function in vivo

The 2023 mouse-focused review stresses that p53 outputs are dose-, tissue-, and context-dependent, and that canonical targets like p21 and Puma may be induced broadly but with distinct kinetics and fate outcomes. This motivates the need for in vivo profiling and reporter models. (pant2023tissuespecificityand pages 3-4)

5) Mouse genetic evidence, statistics, and quantitative findings (recently summarized)

5.1 Essentiality of Mdm2/Mdm4 restraint of p53 (causal genetics)

In mouse genetics, the importance of Mdm2-mediated restraint is supported by the finding that Mdm2 deficiency causes embryonic lethality, which is rescued by deletion of p53; similarly, Mdm4 loss yields p53-dependent embryonic lethality. (pant2023tissuespecificityand pages 3-4, liu2024understandingthecomplexity pages 3-4)

5.2 Quantitative transcriptional induction of p53 targets in vivo

A mouse study summarized in the 2023 review examined acute global Mdm2 loss in adult mice and reported 100% lethality, with widespread induction of canonical p53 targets. Reported p21 induction varied markedly by tissue, including approximately:
- ~190-fold in kidney
- ~40-fold in heart
- ~20-fold in cerebellum, cerebrum, and eye (pant2023tissuespecificityand pages 3-4)

These values provide concrete evidence for strong tissue-dependence of the p53 transcriptional program.

5.3 PTM knock-in mouse models connect molecular regulation to tumor suppression

A 2024 synthesis highlights knock-in mouse models testing acetylation dependence:
- p53-3KR: retains DNA-binding but fails to activate major targets such as p21 and PUMA; yet these mice are described as not tumor prone.
- p53-4KR and p53-5KR: further eliminate regulation of ferroptosis and mTOR-linked outputs and recapitulate tumor susceptibility similar to p53-null mice.
- p53-KQ (acetylation-mimic): shows substantial transcriptional activation and tumor suppression without increasing p53 protein levels. (liu2024understandingthecomplexity pages 3-4)

These mouse genetics are used in the review to argue that specific PTM-controlled branches (including ferroptosis and mTOR regulation) can be critical to p53 tumor suppression in vivo. (liu2024understandingthecomplexity pages 3-4)

5.4 New mouse “real-world” implementations: reporters for fate decisions

The 2024 EMBO Journal resource provides a practical implementation of p53 biology for functional interrogation: fluorescent reporters at Puma/Bbc3 and p21/Cdkn1a enable tracking apoptosis versus arrest/senescence. The study situates Puma and p21 as canonical direct target genes linked to these fates. (lieschke2024mousemodelsto pages 1-2)

6) Current applications and real-world implementations

6.1 In vivo biology and single-cell fate tracking

The Puma and p21 reporter mice (plus FLAG-Trp53 KI) enable:
- cell-type-resolved mapping of p53 activation outcomes,
- identification of context-dependent p53 binding loci and interactors via pulldown,
- discrimination of p53-dependent vs p53-independent activation of these programs in vivo. (lieschke2024mousemodelsto pages 1-2)

6.2 Pharmacologic activation of p53 signaling (preclinical and translational)

For tumors with wild-type p53, therapeutic strategies often aim to liberate p53 from MDM2/MDM4 inhibition. In the mouse-tool paper, nutlin-3a (an MDM2 inhibitor) is used as a p53-activating perturbation in mouse thymocytes and fibroblasts, illustrating how this axis is leveraged experimentally. (lieschke2024mousemodelsto pages 2-3)

A translational expert review provides a broader framing of p53-directed therapy strategies (MDM2/MDM4 inhibition; mutant p53 reactivation; gene therapy and immunotherapy combinations). (hassin2023druggingp53in pages 1-2, hassin2023druggingp53in pages 2-3)

7) Visual evidence (key figure/table)

Pant et al. provide a visual synthesis of physiological stressors (UV/DNA damage, hypoxia, ribosomal dysfunction, inflammation, nutrient deprivation) and effectors/targets including a proposed “universal p53 signature” and examples of tissue-specific targets. (pant2023tissuespecificityand media 74b6a444)

Their table of p53-induced pathologies in mouse tissues summarizes genotype-to-phenotype relationships used to interpret p53 dose effects (e.g., Mdm2/Mdm4 allele perturbations) in vivo. (pant2023tissuespecificityand media 7cd810e2)

Evidence map (compact)

The following table provides a compact evidence map that can be used directly for functional annotation workflows:

Aspect	Key points (mouse p53)	Representative evidence (include citation ids)	Recent sources (year, journal, URL)
Identity / disambiguation	Target verified as mouse Tp53/Trp53, UniProt P02340, encoding cellular tumor antigen p53 in Mus musculus; belongs to the p53 family and should not be conflated with human TP53 or other family members (p63/p73). Mouse literature explicitly distinguishes TRP53 in mice from TP53 in humans.	Mouse-specific review and model papers refer to TRP53/Trp53 and define it as the murine ortholog of TP53 (lieschke2024mousemodelsto pages 1-2, pant2023tissuespecificityand pages 1-2)	2024, The EMBO Journal, https://doi.org/10.1038/s44318-024-00189-z; 2023, Cell Death & Differentiation, https://doi.org/10.1038/s41418-023-01123-2
Molecular function & DNA response element	p53 is primarily a sequence-specific DNA-binding transcription factor. It binds DNA mainly as a tetramer and recognizes response elements built from two decameric half-sites with consensus RRRCWWGYYY; direct targets number roughly >300 in one recent review, while another cites ~500 direct target genes. Core outputs include cell-cycle arrest, apoptosis, senescence, DNA-damage repair, and metabolic adaptation.	Domain/function and RE consensus described in major 2024 review; mouse models paper states homo-tetramer binding to regulatory motifs of ~500 direct targets (liu2024understandingthecomplexity pages 1-3, liu2024understandingthecomplexity pages 3-4, lieschke2024mousemodelsto pages 1-2)	2024, Cancer Cell, https://doi.org/10.1016/j.ccell.2024.04.009; 2024, The EMBO Journal, https://doi.org/10.1038/s44318-024-00189-z
Domain architecture	Conserved p53 architecture comprises TAD1/TAD2, proline-rich domain (PRD), central DNA-binding domain (DBD), tetramerization domain (TD), and C-terminal regulatory domain (CTD). The DBD is well-folded; TAD/CTD are intrinsically disordered and major PTM platforms; TD enables tetramer formation. Mouse-focused review also notes DBD hotspot mutations and TD mutations impair transcriptional activity.	Detailed 5-domain structure and disorder/PTM properties; mouse review summarizes residue ranges and TD/DBD importance (liu2024understandingthecomplexity pages 1-3, pant2023tissuespecificityand pages 1-2)	2024, Cancer Cell, https://doi.org/10.1016/j.ccell.2024.04.009; 2023, Cell Death & Differentiation, https://doi.org/10.1038/s41418-023-01123-2
Subcellular localization & canonical regulation	In unstressed cells p53 is low-abundance with short half-life (~20–30 min) and is controlled largely post-translationally. Mdm2 ubiquitinates p53, maintains low levels, and can export nuclear p53 to the cytoplasm; Mdm4/Mdmx restrains transactivation and cooperates with Mdm2; ARF inhibits/sequesters Mdm2 (including nucleolar sequestration), stabilizing p53. DNA damage signaling (ATM/ATR; p53 S15/S20/S37/S46 phosphorylation) disrupts Mdm2 repression and promotes nuclear accumulation/activation.	Half-life, UV/ATR-MDM2 regulation, ribosomal-stress stabilization, and Mdm2/Mdm4 roles in mouse review; core MDM2/MDMX/ARF logic in 2024 review and RB-E2F-ARF-p53 review (pant2023tissuespecificityand pages 2-3, liu2024understandingthecomplexity pages 3-4, zhou2023expandingrolesof pages 1-2)	2023, Cell Death & Differentiation, https://doi.org/10.1038/s41418-023-01123-2; 2024, Cancer Cell, https://doi.org/10.1016/j.ccell.2024.04.009; 2023, Biology, https://doi.org/10.3390/biology12121511
Key target genes: cell-cycle arrest / senescence	Canonical p53 targets include Cdkn1a/p21 as a major effector of G1/S arrest and senescence; additional arrest-associated targets include 14-3-3σ, GADD45, Reprimo, Prl-3, Ptprv in recent pathway reviews. p21 is repeatedly validated in mouse in vivo systems as a robust p53 readout.	p21 highlighted as canonical murine target in tissue-specific and reporter-mouse studies; broader arrest network reviewed in E2F-RB-p53 article (pant2023tissuespecificityand pages 3-4, lieschke2024mousemodelsto pages 1-2, zhou2023expandingrolesof pages 10-12)	2023, Cell Death & Differentiation, https://doi.org/10.1038/s41418-023-01123-2; 2024, The EMBO Journal, https://doi.org/10.1038/s44318-024-00189-z; 2023, Biology, https://doi.org/10.3390/biology12121511
Key target genes: apoptosis	Canonical apoptotic targets include Bbc3/Puma, Bax, Pmaip1/Noxa, and Apaf1. Mouse studies show PUMA is essential for many p53-induced apoptotic responses, while p21 is critical for arrest/senescence. In reporter knock-in mice, Puma and p21 reporters separately track apoptotic versus arrest programs.	Mouse review and 2024 reporter study directly connect Puma with apoptosis and p21 with arrest; broader pathway review includes Bax/Noxa/Apaf1 (lieschke2024mousemodelsto pages 1-2, lieschke2024mousemodelsto pages 2-3, zhou2023expandingrolesof pages 10-12)	2024, The EMBO Journal, https://doi.org/10.1038/s44318-024-00189-z; 2023, Biology, https://doi.org/10.3390/biology12121511
Key target genes: feedback, metabolism, ferroptosis	Mdm2 is itself a p53 target, creating the core negative-feedback loop. Metabolic targets include GLS2 and SCO2 (promote OXPHOS) and repression of GLUT1/GLUT4. Ferroptosis-associated p53 targets discussed in recent reviews include SLC7A11, VKORC1L1, GLS2, PLTP; acetylation-dependent control of ferroptosis contributes to tumor suppression in mouse models.	Mdm2 feedback loop and metabolic rewiring from mouse review; ferroptosis-target links and acetylation-mouse evidence from 2024 synthesis (pant2023tissuespecificityand pages 2-3, liu2024understandingthecomplexity pages 6-8, liu2024understandingthecomplexity pages 3-4)	2023, Cell Death & Differentiation, https://doi.org/10.1038/s41418-023-01123-2; 2024, Cancer Cell, https://doi.org/10.1016/j.ccell.2024.04.009
Mouse genetic evidence: Mdm2/Mdm4 loss and rescue	Mdm2 knockout causes pre-implantation embryonic lethality that is rescued by p53 deletion; Mdm4 loss also causes p53-dependent embryonic lethality. Acute global Mdm2 deletion in adults can cause 100% lethality with widespread p21/Puma induction; these studies establish Mdm2/Mdm4 as essential physiological restraints on mouse p53.	Explicit rescue and lethality phenotypes summarized in mouse tissue-specific review and major 2024 review (pant2023tissuespecificityand pages 3-4, liu2024understandingthecomplexity pages 3-4)	2023, Cell Death & Differentiation, https://doi.org/10.1038/s41418-023-01123-2; 2024, Cancer Cell, https://doi.org/10.1016/j.ccell.2024.04.009
Mouse genetic evidence: quantitative in vivo transcriptional output	In adult mice with acute Mdm2 loss, p53 target induction is strongly tissue-dependent: p21 increases ~190-fold in kidney, ~40-fold in heart, and ~20-fold in cerebellum/cerebrum/eye; Puma is induced broadly but with tissue-specific kinetics, especially in radiosensitive tissues. These data support strong spatiotemporal context dependence of p53 transcriptional programs.	Quantitative fold-changes and tissue specificity from mouse review (pant2023tissuespecificityand pages 3-4)	2023, Cell Death & Differentiation, https://doi.org/10.1038/s41418-023-01123-2
Mouse genetic evidence: PTM / acetylation knock-ins	PTMs are central regulators of p53 activity. In mouse knock-ins, p53-3KR retains DNA binding but cannot efficiently activate major targets like p21 and PUMA and is not tumor prone; more extensive mutants (p53-4KR/5KR) lose ferroptosis/mTOR-linked tumor suppression and phenocopy p53-null susceptibility; p53-KQ acetylation-mimic mice show strong transcriptional activation/tumor suppression without increased protein abundance.	Knock-in phenotypes summarized in 2024 Cancer Cell review (liu2024understandingthecomplexity pages 3-4)	2024, Cancer Cell, https://doi.org/10.1016/j.ccell.2024.04.009
Tissue specificity / localization of function	p53 functions predominantly in the nucleus as a transcription factor, but outputs are markedly cell- and tissue-specific. Radiosensitive tissues such as thymus, bone marrow, spleen, intestinal epithelium preferentially undergo apoptosis, whereas other tissues show stronger growth arrest. A recent figure summarizes physiological stressors and a universal 8-gene p53 signature with tissue-specific targets.	Tissue-specific murine review and extracted figure context (pant2023tissuespecificityand pages 3-4, pant2023tissuespecificityand media 74b6a444)	2023, Cell Death & Differentiation, https://doi.org/10.1038/s41418-023-01123-2
Applications: mouse tools	New mouse tools include triple-FLAG Trp53 knock-in mice for p53 pull-downs and Puma-tdTomato / p21-GFP reporter mice to visualize p53-induced apoptosis or arrest/senescence in vivo. FLAG-tagged p53 remained functional in assays, including target-gene induction and responses to nutlin-3a, etoposide, irradiation, and senescence-inducing treatments.	2024 EMBO resource paper describing functional FLAG and reporter mice (lieschke2024mousemodelsto pages 1-2, lieschke2024mousemodelsto pages 2-3)	2024, The EMBO Journal, https://doi.org/10.1038/s44318-024-00189-z
Applications: pharmacology / translational relevance	In tumors retaining wild-type p53, MDM2 inhibitors (e.g., nutlin-3a in mouse-cell assays) activate p53. Broader translational strategies include releasing wild-type p53 from MDM2/MDM4 inhibition, restoring mutant p53 conformation/function, gene therapy, and immunotherapy combinations. p53 remains challenging to drug because it is a nuclear transcription factor, but it is a major therapeutic focus.	Nutlin-responsive mouse assays in FLAG-Trp53 study; translational review outlines p53 drugging logic and challenges (lieschke2024mousemodelsto pages 2-3, hassin2023druggingp53in pages 1-2, hassin2023druggingp53in pages 2-3)	2024, The EMBO Journal, https://doi.org/10.1038/s44318-024-00189-z; 2023, Nature Reviews Drug Discovery, https://doi.org/10.1038/s41573-022-00571-8

Table: This table summarizes verified identity, core molecular function, regulation, target genes, mouse genetic evidence, and translational relevance for mouse Tp53/Trp53 (UniProt P02340). It is designed as a compact evidence map for functional annotation using recent authoritative sources.

8) Summary functional annotation (mouse Tp53 / p53)

Mouse Tp53 (Trp53; UniProt P02340) encodes p53, a stress-activated, sequence-specific DNA-binding transcription factor that binds canonical response elements (RRRCWWGYYY half-sites) as a tetramer and regulates a large transcriptional program (hundreds of direct targets, thousands indirectly). Its activity is controlled by domain-structured interactions and extensive PTMs, with MDM2/MDM4 serving as principal negative regulators and ARF as an upstream activator via MDM2 inhibition. In vivo, p53 triggers cell-cycle arrest/senescence prominently via p21 (Cdkn1a) and apoptosis prominently via Puma (Bbc3), with strong tissue-dependent outcomes and quantitative differences in target induction across organs. Recent (2023–2024) work emphasizes context specificity, PTM-defined functional branches (including metabolism and ferroptosis), and newly developed mouse knock-in reporter systems that enable direct observation of p53-driven fate decisions in situ. (pant2023tissuespecificityand pages 1-2, liu2024understandingthecomplexity pages 3-4, pant2023tissuespecificityand pages 3-4, lieschke2024mousemodelsto pages 1-2)

References

(pant2023tissuespecificityand pages 1-2): Vinod Pant, Chang Sun, and Guillermina Lozano. Tissue specificity and spatio-temporal dynamics of the p53 transcriptional program. Cell Death & Differentiation, 30:897-905, Feb 2023. URL: https://doi.org/10.1038/s41418-023-01123-2, doi:10.1038/s41418-023-01123-2. This article has 24 citations and is from a domain leading peer-reviewed journal.
(lieschke2024mousemodelsto pages 1-2): Elizabeth Lieschke, Annabella F Thomas, Andrew Kueh, Georgia K Atkin-Smith, Pedro L Baldoni, John E. La Marca, Savannah Young, Allan Shuai Huang, Aisling M. Ross, Lauren Whelan, Deeksha Kaloni, Lin Tai, Gordon K Smyth, Marco J Herold, Edwin D. Hawkins, Andreas Strasser, and Gemma L. Kelly. Mouse models to investigate in situ cell fate decisions induced by p53. The EMBO Journal, 43:4406-4436, Aug 2024. URL: https://doi.org/10.1038/s44318-024-00189-z, doi:10.1038/s44318-024-00189-z. This article has 5 citations.
(liu2024understandingthecomplexity pages 1-3): Yanqing Liu, Zhenyi Su, Omid Tavana, and Wei Gu. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell, 42:946-967, Jun 2024. URL: https://doi.org/10.1016/j.ccell.2024.04.009, doi:10.1016/j.ccell.2024.04.009. This article has 471 citations and is from a highest quality peer-reviewed journal.
(hassin2023druggingp53in pages 1-2): Ori Hassin and Moshe Oren. Drugging p53 in cancer: one protein, many targets. Nature Reviews. Drug Discovery, 22:127-144, Oct 2023. URL: https://doi.org/10.1038/s41573-022-00571-8, doi:10.1038/s41573-022-00571-8. This article has 753 citations.
(liu2024understandingthecomplexity pages 3-4): Yanqing Liu, Zhenyi Su, Omid Tavana, and Wei Gu. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell, 42:946-967, Jun 2024. URL: https://doi.org/10.1016/j.ccell.2024.04.009, doi:10.1016/j.ccell.2024.04.009. This article has 471 citations and is from a highest quality peer-reviewed journal.
(zhou2023expandingrolesof pages 1-2): Yaxuan Zhou, Rinka Nakajima, Mashiro Shirasawa, Mariana Fikriyanti, Lin Zhao, Ritsuko Iwanaga, Andrew P. Bradford, Kenta Kurayoshi, Keigo Araki, and Kiyoshi Ohtani. Expanding roles of the e2f-rb-p53 pathway in tumor suppression. Biology, 12:1511, Dec 2023. URL: https://doi.org/10.3390/biology12121511, doi:10.3390/biology12121511. This article has 49 citations.
(pant2023tissuespecificityand media 74b6a444): Vinod Pant, Chang Sun, and Guillermina Lozano. Tissue specificity and spatio-temporal dynamics of the p53 transcriptional program. Cell Death & Differentiation, 30:897-905, Feb 2023. URL: https://doi.org/10.1038/s41418-023-01123-2, doi:10.1038/s41418-023-01123-2. This article has 24 citations and is from a domain leading peer-reviewed journal.
(pant2023tissuespecificityand pages 2-3): Vinod Pant, Chang Sun, and Guillermina Lozano. Tissue specificity and spatio-temporal dynamics of the p53 transcriptional program. Cell Death & Differentiation, 30:897-905, Feb 2023. URL: https://doi.org/10.1038/s41418-023-01123-2, doi:10.1038/s41418-023-01123-2. This article has 24 citations and is from a domain leading peer-reviewed journal.
(pant2023tissuespecificityand pages 3-4): Vinod Pant, Chang Sun, and Guillermina Lozano. Tissue specificity and spatio-temporal dynamics of the p53 transcriptional program. Cell Death & Differentiation, 30:897-905, Feb 2023. URL: https://doi.org/10.1038/s41418-023-01123-2, doi:10.1038/s41418-023-01123-2. This article has 24 citations and is from a domain leading peer-reviewed journal.
(zhou2023expandingrolesof pages 10-12): Yaxuan Zhou, Rinka Nakajima, Mashiro Shirasawa, Mariana Fikriyanti, Lin Zhao, Ritsuko Iwanaga, Andrew P. Bradford, Kenta Kurayoshi, Keigo Araki, and Kiyoshi Ohtani. Expanding roles of the e2f-rb-p53 pathway in tumor suppression. Biology, 12:1511, Dec 2023. URL: https://doi.org/10.3390/biology12121511, doi:10.3390/biology12121511. This article has 49 citations.
(liu2024understandingthecomplexity pages 6-8): Yanqing Liu, Zhenyi Su, Omid Tavana, and Wei Gu. Understanding the complexity of p53 in a new era of tumor suppression. Cancer Cell, 42:946-967, Jun 2024. URL: https://doi.org/10.1016/j.ccell.2024.04.009, doi:10.1016/j.ccell.2024.04.009. This article has 471 citations and is from a highest quality peer-reviewed journal.
(hassin2023druggingp53in pages 2-3): Ori Hassin and Moshe Oren. Drugging p53 in cancer: one protein, many targets. Nature Reviews. Drug Discovery, 22:127-144, Oct 2023. URL: https://doi.org/10.1038/s41573-022-00571-8, doi:10.1038/s41573-022-00571-8. This article has 753 citations.
(lieschke2024mousemodelsto pages 2-3): Elizabeth Lieschke, Annabella F Thomas, Andrew Kueh, Georgia K Atkin-Smith, Pedro L Baldoni, John E. La Marca, Savannah Young, Allan Shuai Huang, Aisling M. Ross, Lauren Whelan, Deeksha Kaloni, Lin Tai, Gordon K Smyth, Marco J Herold, Edwin D. Hawkins, Andreas Strasser, and Gemma L. Kelly. Mouse models to investigate in situ cell fate decisions induced by p53. The EMBO Journal, 43:4406-4436, Aug 2024. URL: https://doi.org/10.1038/s44318-024-00189-z, doi:10.1038/s44318-024-00189-z. This article has 5 citations.
(pant2023tissuespecificityand media 7cd810e2): Vinod Pant, Chang Sun, and Guillermina Lozano. Tissue specificity and spatio-temporal dynamics of the p53 transcriptional program. Cell Death & Differentiation, 30:897-905, Feb 2023. URL: https://doi.org/10.1038/s41418-023-01123-2, doi:10.1038/s41418-023-01123-2. This article has 24 citations and is from a domain leading peer-reviewed journal.

Citations

pant2023tissuespecificityand pages 1-2
liu2024understandingthecomplexity pages 3-4
liu2024understandingthecomplexity pages 1-3
zhou2023expandingrolesof pages 1-2
lieschke2024mousemodelsto pages 1-2
zhou2023expandingrolesof pages 10-12
pant2023tissuespecificityand pages 2-3
liu2024understandingthecomplexity pages 6-8
pant2023tissuespecificityand pages 3-4
lieschke2024mousemodelsto pages 2-3
https://doi.org/10.1038/s44318-024-00189-z;
https://doi.org/10.1038/s41418-023-01123-2
https://doi.org/10.1016/j.ccell.2024.04.009;
https://doi.org/10.1038/s44318-024-00189-z
https://doi.org/10.1038/s41418-023-01123-2;
https://doi.org/10.3390/biology12121511
https://doi.org/10.1016/j.ccell.2024.04.009
https://doi.org/10.1038/s41573-022-00571-8
https://doi.org/10.1038/s41418-023-01123-2,
https://doi.org/10.1038/s44318-024-00189-z,
https://doi.org/10.1016/j.ccell.2024.04.009,
https://doi.org/10.1038/s41573-022-00571-8,
https://doi.org/10.3390/biology12121511,

Bioreason Rl Review

(Trp53-bioreason-rl-review.md)

BioReason-Pro RL Review: Trp53 (mouse)

Source: Trp53-deep-research-bioreason-rl.md

Correctness: 5/5
Completeness: 4/5

Functional Summary Review

The BioReason functional summary is accurate and well-articulated:

A nuclear, tetramer-forming transcriptional regulator that uses an N-terminal activation module and a central site-recognition core to control RNA polymerase II-dependent gene programs. By assembling into a cooperative homotetramer, it binds specific promoter elements, recruits chromatin-modifying cofactors, and toggles between activation and repression to enforce checkpoint pathways that govern cell cycle control and trigger apoptosis under stress.

This correctly identifies: (1) the nuclear localization (GO:0005634), (2) the tetramerization domain and cooperative DNA binding, (3) the N-terminal transactivation domain, (4) the central DNA-binding domain, (5) RNA polymerase II transcriptional regulation (GO:0000981), (6) the dual activator/repressor function, (7) cell cycle control (GO:0051726), and (8) apoptosis induction (GO:0006915). The curated review's IBA annotations include GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0042771 (intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator), and GO:0042981 (regulation of apoptotic process).

The UniProt summary for mouse Trp53 describes it as a "tumor suppressor" that "induces growth arrest or apoptosis" and acts as "a trans-activating protein that acts downstream of a signal mediated by a DNA damage-stress pathway" -- all consistent with the BioReason summary.

The mention of "toggling between activation and repression" is a good nuance that captures the dual transcriptional function. The description of "checkpoint pathways" accurately reflects the DNA damage checkpoint role.

Minor gaps: The summary does not mention the specific DNA damage response context, the MDM2-mediated regulation of p53 stability, post-translational modifications that activate p53, or its roles in senescence and autophagy. The metabolic reprogramming functions (glycolysis regulation, ferroptosis) established for p53 are also absent.

Comparison with interpro2go:

The curated review has two GO_REF:0000002 annotations: GO:0006915 (apoptotic process) and GO:0051262 (protein tetramerization). BioReason's summary correctly captures both -- the apoptotic role and the tetramer formation. BioReason adds substantial value by explaining the mechanistic link between tetramerization and cooperative DNA binding, and by describing the dual activator/repressor function. The interpro2go annotations are basic; BioReason weaves them into a coherent functional narrative.

Notes on thinking trace

The trace provides careful analysis of the p53-family domain architecture: transactivation domain, DNA-binding domain (with the conserved central site), and tetramerization domain. The mechanistic model of a tetrameric transcriptional switch that senses stress and enforces checkpoints is accurate. The hypothesis about E3 ubiquitin ligase partners (MDM2) and checkpoint kinases (ATM/ATR/CHK1/CHK2) is well-supported.

📄 View Raw YAML

id: P02340
gene_symbol: Trp53
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: 'Mouse Trp53 encodes tumor suppressor p53, a stress-activated, sequence-specific DNA-binding transcription factor. p53 binds response elements as a tetramer and regulates gene programs controlling cell-cycle arrest, apoptosis, senescence, DNA repair, metabolism, and other stress responses. Its core role is nuclear transcriptional control, with additional context-dependent mitochondrial, cytoplasmic, and tissue-specific outputs.'
existing_annotations:
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: regulation of apoptotic process is a broad downstream p53 cell-fate annotation rather than the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: p53 can induce apoptotic programs after stress, but broad apoptosis terms should be retained as non-core because the core Trp53 function is sequence-specific DNA-binding transcriptional regulation.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Canonical apoptotic targets include Bbc3/Puma, Bax, Pmaip1/Noxa, and Apaf1.
- term:
    id: GO:1990841
    label: promoter-specific chromatin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: promoter-specific chromatin binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: chromatin is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: transcription cis-regulatory region binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: DNA-binding transcription factor activity is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cytoplasm is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: mitochondrial matrix is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: endoplasmic reticulum is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: centrosome is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: regulation of DNA-templated transcription is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: apoptotic process is a broad downstream p53 cell-fate annotation rather than the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: p53 can induce apoptotic programs after stress, but broad apoptosis terms should be retained as non-core because the core Trp53 function is sequence-specific DNA-binding transcriptional regulation.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Canonical apoptotic targets include Bbc3/Puma, Bax, Pmaip1/Noxa, and Apaf1.
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: response to oxidative stress is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: response to xenobiotic stimulus is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0009411
    label: response to UV
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: response to UV is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0010165
    label: response to X-ray
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: response to X-ray is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0016605
    label: PML body
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: PML body is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0048468
    label: cell development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: cell development is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0051053
    label: negative regulation of DNA metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: negative regulation of DNA metabolic process is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0051262
    label: protein tetramerization
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: protein tetramerization is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0097190
    label: apoptotic signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: apoptotic signaling pathway is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0097371
    label: MDM2/MDM4 family protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: MDM2/MDM4 family protein binding is a valid p53 regulatory interaction, but it belongs outside the core function set.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because MDM2/MDM4 binding controls p53 stability and activity, whereas the core Trp53 function is sequence-specific transcriptional regulation of stress-response targets.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53.
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: MDM4/MDMX restrains p53 transactivation and forms a heterodimer with MDM2 to enhance p53 degradation.
- term:
    id: GO:2001242
    label: regulation of intrinsic apoptotic signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: regulation of intrinsic apoptotic signaling pathway is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10329544
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11181729
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11274052
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11781573
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16151013
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16480949
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16697373
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17535810
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17936560
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18025262
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18303029
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18359851
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18448518
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18695251
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19011633
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19556538
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20621096
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20697359
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20708612
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20832751
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21057544
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21122074
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21670284
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21741598
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21857681
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21909133
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22056770
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22726440
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23123091
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23980194
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24116158
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25117711
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26960425
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28536627
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37025149
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9194565
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: chromatin is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: DNA-binding transcription factor activity, RNA polymerase II-specific is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0000987
    label: cis-regulatory region sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cis-regulatory region sequence-specific DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0001046
    label: core promoter sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: core promoter sequence-specific DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0001094
    label: TFIID-class transcription factor complex binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: TFIID-class transcription factor complex binding is a documented p53 regulatory interaction, but not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because p53 is primarily curated here as a sequence-specific DNA-binding transcription factor; TFIID/TAF binding is a cofactor interaction that modulates transcriptional regulation.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex.
- term:
    id: GO:0001223
    label: transcription coactivator binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: transcription coactivator binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0001227
    label: DNA-binding transcription repressor activity, RNA polymerase II-specific
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: DNA-binding transcription repressor activity, RNA polymerase II-specific is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0001228
    label: DNA-binding transcription activator activity, RNA polymerase II-specific
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: DNA-binding transcription activator activity, RNA polymerase II-specific is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0002020
    label: protease binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protease binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0002039
    label: p53 binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: p53 binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0002244
    label: hematopoietic progenitor cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: hematopoietic progenitor cell differentiation is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: chromatin binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0003730
    label: mRNA 3'-UTR binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mRNA 3'-UTR binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005507
    label: copper ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Copper ion binding is not supported for mouse p53 by the cited evidence; UniProt documents Zn(2+) binding instead.
    action: MODIFY
    reason: >-
      Replace the unsupported copper-binding term with GO:0008270 zinc ion binding, the metal cofactor documented for p53.
    proposed_replacement_terms:
    - id: GO:0008270
      label: zinc ion binding
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: nucleoplasm is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: transcription regulator complex is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: nucleolus is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mitochondrion is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cytosol is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0006289
    label: nucleotide-excision repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: nucleotide-excision repair is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: autophagy is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Ras protein signal transduction is not the direct molecular activity of p53. It
      may reflect downstream pathway crosstalk from stress and proliferation programs,
      but it overstates the core p53 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      p53 is a sequence-specific transcription factor and stress-response regulator.
      A broad Ras signaling annotation is too pathway-level and indirect for the
      available evidence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0008104
    label: intracellular protein localization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Intracellular protein localization is an inferred broad process annotation. p53 itself is regulated by MDM2-mediated nuclear export and stress-dependent nuclear accumulation, but this does not make protein-localization control a core p53 output.
    action: MARK_AS_OVER_ANNOTATED
    reason: The evidence supports p53 subcellular regulation, not a direct core role for p53 in intracellular protein localization.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Functionally, p53 acts predominantly in the nucleus as a transcription factor. Consistent with this, MDM2-mediated regulation explicitly includes export of nuclear p53 to the cytoplasm, and stress-dependent disruption of this repression allows nuclear accumulation and transcriptional activation.
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: 'GO; GO:0008104; P:intracellular protein localization; ISO:GO_Central.'
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of cell population proliferation is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0009299
    label: mRNA transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mRNA transcription is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0010332
    label: response to gamma radiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to gamma radiation is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of gene expression is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0016032
    label: viral process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: viral process is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0016363
    label: nuclear matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: nuclear matrix is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: nuclear body is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: enzyme binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0030308
    label: negative regulation of cell growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of cell growth is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0030330
    label: DNA damage response, signal transduction by p53 class mediator
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: DNA damage response, signal transduction by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0030971
    label: receptor tyrosine kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Receptor tyrosine kinase binding is not supported as a direct retained p53
      molecular function in the reviewed evidence. UniProt notes many p53 regulatory
      interactions, including non-receptor PTK2/PTK2B contexts, but not a well-supported
      receptor tyrosine kinase binding activity.
    action: REMOVE
    reason: >-
      The annotation appears to be an over-propagated generic binding claim. It is not
      justified by the Falcon synthesis or UniProt evidence for p53's core DNA-binding
      transcription factor activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2. Interacts with PTK2B/PYK2.
- term:
    id: GO:0031571
    label: mitotic G1 DNA damage checkpoint signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mitotic G1 DNA damage checkpoint signaling is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Ubiquitin protein ligase binding is a valid non-core regulatory interaction for p53 stability control.
    action: KEEP_AS_NON_CORE
    reason: >-
      p53 binding to E3 ligases such as MDM2 and FATS regulates p53 stability, but this is regulatory context rather than the core p53 transcription factor activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: MDM2 is a major negative regulator; it ubiquitinates p53 to maintain low basal levels.
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Interacts with C10orf90/FATS; the interaction inhibits binding of TP53 and MDM2.
- term:
    id: GO:0032211
    label: negative regulation of telomere maintenance via telomerase
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of telomere maintenance via telomerase is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein-containing complex is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0033209
    label: tumor necrosis factor-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: tumor necrosis factor-mediated signaling pathway is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0034644
    label: cellular response to UV
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to UV is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0036310
    label: ATP-dependent DNA/DNA annealing activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      ATP-dependent DNA/DNA annealing activity is not supported by the reviewed mouse p53 evidence.
    action: REMOVE
    reason: >-
      The evidence supports sequence-specific DNA binding and transcriptional regulation, not ATP-dependent DNA annealing enzyme activity.
- term:
    id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: identical protein binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0042826
    label: histone deacetylase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Histone deacetylase binding is present as an orthology-derived interaction annotation and fits p53 post-translational regulation by deacetylases such as SIRT1, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as a supported regulatory interaction context rather than treating histone deacetylase binding as a core p53 function.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Deacetylation of Lys-379 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence.
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: 'GO; GO:0042826; F:histone deacetylase binding; ISO:GO_Central.'
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: positive regulation of apoptotic process is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Negative regulation of apoptotic process is an inferred annotation that does not match the main p53 apoptotic program; p53 is better supported as a positive regulator of intrinsic apoptosis through targets such as Puma/Bbc3, Bax, Noxa, and Apaf1.
    action: MARK_AS_OVER_ANNOTATED
    reason: The cited support favors p53-induced apoptosis, not a core anti-apoptotic role for Trp53.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Canonical apoptotic targets include Bbc3/Puma, Bax, Pmaip1/Noxa, and Apaf1. Mouse studies show PUMA is essential for many p53-induced apoptotic responses, while p21 is critical for arrest/senescence.
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: 'GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.'
- term:
    id: GO:0045815
    label: transcription initiation-coupled chromatin remodeling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: transcription initiation-coupled chromatin remodeling is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of DNA-templated transcription is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of DNA-templated transcription is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0045899
    label: positive regulation of RNA polymerase II transcription preinitiation complex assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of RNA polymerase II transcription preinitiation complex assembly is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0046677
    label: response to antibiotic
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Response to antibiotic is a broad treatment-response phenotype, not a direct p53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: This can be retained as a context-specific stress-response output, but it should not be core for Trp53.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent.
- term:
    id: GO:0046982
    label: protein heterodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Protein heterodimerization activity is not supported as a direct p53 activity; p53 forms homodimers and homotetramers.
    action: REMOVE
    reason: The reviewed evidence supports p53 homodimerization/homotetrameric DNA binding rather than heterodimerization.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Forms homodimers and homotetramers. Binds DNA as a homotetramer.
- term:
    id: GO:0048147
    label: negative regulation of fibroblast proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of fibroblast proliferation is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0048539
    label: bone marrow development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: bone marrow development is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein-folding chaperone binding is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0051721
    label: protein phosphatase 2A binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein phosphatase 2A binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0051726
    label: regulation of cell cycle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of cell cycle is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0060218
    label: hematopoietic stem cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: hematopoietic stem cell differentiation is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: RNA polymerase II-specific DNA-binding transcription factor binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0065003
    label: protein-containing complex assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein-containing complex assembly is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cellular response to hypoxia is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0071466
    label: cellular response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to xenobiotic stimulus is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0071479
    label: cellular response to ionizing radiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to ionizing radiation is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0071480
    label: cellular response to gamma radiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to gamma radiation is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0072331
    label: signal transduction by p53 class mediator
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: signal transduction by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0072332
    label: intrinsic apoptotic signaling pathway by p53 class mediator
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: intrinsic apoptotic signaling pathway by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0072717
    label: cellular response to actinomycin D
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to actinomycin D is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0090200
    label: positive regulation of release of cytochrome c from mitochondria
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of release of cytochrome c from mitochondria is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0090399
    label: replicative senescence
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: replicative senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0090403
    label: oxidative stress-induced premature senescence
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: oxidative stress-induced premature senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0097252
    label: oligodendrocyte apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Oligodendrocyte apoptotic process is a tissue-specific p53 apoptotic output, not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because p53 apoptotic programs are highly tissue- and stress-specific; the core activity is DNA-binding transcriptional regulation of cell-fate targets.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Tissue specificity / localization of function | p53 functions predominantly in the nucleus as a transcription factor, but outputs are markedly cell- and tissue-specific.
- term:
    id: GO:0097718
    label: disordered domain specific binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: disordered domain specific binding is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0140296
    label: general transcription initiation factor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: general transcription initiation factor binding is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0140677
    label: molecular function activator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: molecular function activator activity is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0140693
    label: molecular condensate scaffold activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Molecular condensate scaffold activity has UniProt support through p53 condensate regulation, but it is specialized regulatory biophysics rather than the core annotation.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because phase-separation behavior modulates p53 regulation while the main curated function remains DNA-binding transcriptional control.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Phosphorylation at Ser-389 regulates its ability to undergo liquid-liquid phase separation by increasing fluidity of TP53/p53 condensates
- term:
    id: GO:1900119
    label: positive regulation of execution phase of apoptosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of execution phase of apoptosis is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:1902895
    label: positive regulation of miRNA transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of miRNA transcription is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:1903451
    label: negative regulation of G1 to G0 transition
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of G1 to G0 transition is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:1905856
    label: negative regulation of pentose-phosphate shunt
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Negative regulation of the pentose-phosphate shunt is supported by a specific G6PD-containing complex, but it is a specialized metabolic branch of p53 activity.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because this metabolic regulation is context-specific and downstream of p53 regulatory interactions rather than the central DNA-binding transcription factor function.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Forms a ternary complex with ALDOB and G6PD; this interaction is direct. ALDOB stabilizes the complex inhibiting G6PD activity and keeping oxidative pentose phosphate metabolism in check.
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Metabolic targets include GLS2 and SCO2 (promote OXPHOS) and repression of GLUT1/GLUT4.
- term:
    id: GO:1990841
    label: promoter-specific chromatin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: promoter-specific chromatin binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:2000379
    label: positive regulation of reactive oxygen species metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of reactive oxygen species metabolic process is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:2000774
    label: positive regulation of cellular senescence
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cellular senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:2001244
    label: positive regulation of intrinsic apoptotic signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of intrinsic apoptotic signaling pathway is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0140693
    label: molecular condensate scaffold activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Molecular condensate scaffold activity has UniProt support through p53 condensate regulation, but it is specialized regulatory biophysics rather than the core annotation.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because phase-separation behavior modulates p53 regulation while the main curated function remains DNA-binding transcriptional control.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Phosphorylation at Ser-389 regulates its ability to undergo liquid-liquid phase separation by increasing fluidity of TP53/p53 condensates
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:16407291
  review:
    summary: p53 positively regulates transcription of PUMA and NOXA during ER stress in MEFs.
    action: ACCEPT
    reason: PMID:16407291 directly supports p53-dependent transcriptional activation of pro-apoptotic targets in this context.
    supported_by:
    - reference_id: PMID:16407291
      supporting_text: ER stress selectively activates BH3-only proteins PUMA and NOXA at the transcript level through the tumor suppressor gene p53.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: PMID:30089260
  review:
    summary: positive regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
    supported_by:
    - reference_id: PMID:30089260
      supporting_text: LRP1 transcript expression is upregulated in response to both sub-lethal and lethal
        doses of p53-activating stress
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: PMID:30089260
  review:
    summary: regulation of transcription by RNA polymerase II is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
    supported_by:
    - reference_id: PMID:30089260
      supporting_text: Our results define a negative feedback loop involving the p53-regulated coding gene
        LRP1 and p53-regulated miRNA genes.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: ISS
  original_reference_id: PMID:30089260
  review:
    summary: DNA damage response is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
    supported_by:
    - reference_id: PMID:30089260
      supporting_text: LRP1 transcript expression is upregulated in response to both sub-lethal and lethal
        doses of p53-activating stress
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9816449
  review:
    summary: nucleoplasm is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:2000774
    label: positive regulation of cellular senescence
  evidence_type: IMP
  original_reference_id: PMID:10562313
  review:
    summary: positive regulation of cellular senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: cellular senescence is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0036310
    label: ATP-dependent DNA/DNA annealing activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ATP-dependent DNA/DNA annealing activity is not supported by the reviewed mouse p53 evidence.
    action: REMOVE
    reason: The evidence supports sequence-specific DNA binding and transcriptional regulation, not ATP-dependent DNA annealing enzyme activity.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: ISS
  original_reference_id: PMID:30089260
  review:
    summary: chromatin is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
    supported_by:
    - reference_id: PMID:30089260
      supporting_text: Here, we identify low-density lipoprotein receptor-related protein 1 (LRP1), a
        transmembrane endocytic receptor, as a p53 target gene.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: centrosome is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of apoptotic process is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:15532030
  review:
    summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:2001244
    label: positive regulation of intrinsic apoptotic signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of intrinsic apoptotic signaling pathway is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0062100
    label: positive regulation of programmed necrotic cell death
  evidence_type: IMP
  original_reference_id: PMID:27258785
  review:
    summary: PMID:27258785 supports p53-dependent promotion of programmed necrosis in cardiomyocytes through the NRF-miR-873-RIPK1/RIPK3 axis.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because this is a cardiomyocyte ischemia/reperfusion output of p53 transcriptional regulation rather than the general core Trp53 function.
    supported_by:
    - reference_id: PMID:27258785
      supporting_text: P53 regulates cardiomyocytes necrosis and myocardial I/R injury through NRF and miR-873.
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:24240685
  review:
    summary: Ubiquitin protein ligase binding is a valid non-core regulatory interaction for p53 stability control.
    action: KEEP_AS_NON_CORE
    reason: p53 binding to E3 ligases such as MDM2 and FATS regulates p53 stability, but this is regulatory context rather than the core p53 transcription factor activity.
    supported_by:
    - reference_id: PMID:24240685
      supporting_text: FATS acts as a p53 activator by inhibiting Mdm2 binding to p53
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: MDM2 is a major negative regulator; it ubiquitinates p53 to maintain low basal levels.
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Interacts with C10orf90/FATS; the interaction inhibits binding of TP53 and MDM2.
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:24051492
  review:
    summary: PMID:24051492 directly links p53 to Per2 promoter binding, transcriptional repression, and mouse circadian behavior.
    action: ACCEPT
    reason: PMID:24051492 directly supports p53 binding to the Per2 promoter and repression of BMAL1/CLOCK-mediated Per2 transcription.
    supported_by:
    - reference_id: PMID:24051492
      supporting_text: p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK.
    - reference_id: PMID:24051492
      supporting_text: The p53−/− mouse period lengths were 22.8 ± 0.1 h
- term:
    id: GO:1990841
    label: promoter-specific chromatin binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: promoter-specific chromatin binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
  evidence_type: IDA
  original_reference_id: PMID:16213212
  review:
    summary: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0071479
    label: cellular response to ionizing radiation
  evidence_type: IDA
  original_reference_id: PMID:16213212
  review:
    summary: cellular response to ionizing radiation is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22262176
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:22262176
  review:
    summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:23629966
  review:
    summary: negative regulation of DNA-templated transcription is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
    supported_by:
    - reference_id: PMID:23629966
      supporting_text: p53 also suppressed Bmf expression in response to other cell death-stimulating agents,
        including ultraviolet radiation and histone deacetylase inhibitors.
- term:
    id: GO:0060333
    label: type II interferon-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:23629966
  review:
    summary: type II interferon-mediated signaling pathway is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16407291
  review:
    summary: The PMID:16407291 MEF evidence directly reports nuclear p53 during ER stress.
    action: ACCEPT
    reason: This supports nuclear localization in the context of the ER-stress apoptotic response.
    supported_by:
    - reference_id: PMID:16407291
      supporting_text: In multiple MEF lines, p53 is primarily nuclear and its level is elevated upon ER stress.
- term:
    id: GO:0070059
    label: intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
  evidence_type: IMP
  original_reference_id: PMID:16407291
  review:
    summary: ER stress-induced apoptosis is directly supported in MEFs and is partially p53-dependent through PUMA and NOXA activation.
    action: ACCEPT
    reason: PMID:16407291 shows p53 contributes to ER stress-induced apoptosis by transcriptionally activating PUMA and NOXA in MEFs.
    supported_by:
    - reference_id: PMID:16407291
      supporting_text: In p53(-/-) MEFs, ER stress-induced apoptosis is partially suppressed.
- term:
    id: GO:0007623
    label: circadian rhythm
  evidence_type: IEP
  original_reference_id: PMID:24051492
  review:
    summary: PMID:24051492 directly links p53 to Per2 promoter binding, transcriptional repression, and mouse circadian behavior.
    action: KEEP_AS_NON_CORE
    reason: The paper supports p53 influence on circadian rhythm behavior, but this is a context-specific organismal output, not core molecular function.
    supported_by:
    - reference_id: PMID:24051492
      supporting_text: p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK.
    - reference_id: PMID:24051492
      supporting_text: The p53−/− mouse period lengths were 22.8 ± 0.1 h
- term:
    id: GO:0043153
    label: entrainment of circadian clock by photoperiod
  evidence_type: IMP
  original_reference_id: PMID:24051492
  review:
    summary: PMID:24051492 supports altered light-cue phase-shift behavior in p53-null mice, downstream of p53 repression of Per2.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because the light-entrainment phenotype is an organismal circadian output, while the direct p53 activity is promoter binding and transcriptional repression.
    supported_by:
    - reference_id: PMID:24051492
      supporting_text: phase shift response to a light cue displays an enhanced phase delay response during free running conditions
    - reference_id: PMID:24051492
      supporting_text: p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:24051492
  review:
    summary: PMID:24051492 directly links p53 to Per2 promoter binding, transcriptional repression, and mouse circadian behavior.
    action: ACCEPT
    reason: PMID:24051492 directly supports p53 binding to the Per2 promoter and repression of BMAL1/CLOCK-mediated Per2 transcription.
    supported_by:
    - reference_id: PMID:24051492
      supporting_text: p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK.
    - reference_id: PMID:24051492
      supporting_text: The p53−/− mouse period lengths were 22.8 ± 0.1 h
- term:
    id: GO:0048512
    label: circadian behavior
  evidence_type: IMP
  original_reference_id: PMID:24051492
  review:
    summary: PMID:24051492 directly links p53 to Per2 promoter binding, transcriptional repression, and mouse circadian behavior.
    action: KEEP_AS_NON_CORE
    reason: The paper supports altered circadian behavior in p53-null mice, but this is a context-specific phenotype, not core molecular function.
    supported_by:
    - reference_id: PMID:24051492
      supporting_text: p53 directly binds to the Per2 promoter and represses its transcriptional activation by BMAL1/CLOCK.
    - reference_id: PMID:24051492
      supporting_text: The p53−/− mouse period lengths were 22.8 ± 0.1 h
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:12667443
  review:
    summary: mitochondrion is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0097252
    label: oligodendrocyte apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Oligodendrocyte apoptotic process is a tissue-specific p53 apoptotic output, not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because p53 apoptotic programs are highly tissue- and stress-specific; the core activity is DNA-binding transcriptional regulation of cell-fate targets.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Tissue specificity / localization of function | p53 functions predominantly in the nucleus as a transcription factor, but outputs are markedly cell- and tissue-specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20599664
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0008340
    label: determination of adult lifespan
  evidence_type: IMP
  original_reference_id: PMID:20818388
  review:
    summary: determination of adult lifespan is supported as a context-specific p53 output or phenotype, but it is not the core molecular function of Trp53.
    action: KEEP_AS_NON_CORE
    reason: p53 has broad tissue- and stress-specific downstream effects; this annotation can be retained as non-core rather than treated as the primary evolved activity.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
  evidence_type: IMP
  original_reference_id: PMID:20818388
  review:
    summary: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0070245
    label: positive regulation of thymocyte apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:20818388
  review:
    summary: Positive regulation of thymocyte apoptotic process is a tissue-specific p53 apoptotic output, not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because thymocyte apoptosis is a cell-type-specific consequence of p53 activation; the core activity is DNA-binding transcriptional regulation of stress-response targets.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Radiosensitive tissues such as thymus, bone marrow, spleen, intestinal epithelium preferentially undergo apoptosis
    - reference_id: PMID:20818388
      supporting_text: p53-dependent apoptosis after DNA damage
- term:
    id: GO:0097371
    label: MDM2/MDM4 family protein binding
  evidence_type: IPI
  original_reference_id: PMID:20818388
  review:
    summary: MDM2/MDM4 family protein binding is a valid p53 regulatory interaction, but it belongs outside the core function set.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because MDM2/MDM4 binding controls p53 stability and activity, whereas the core Trp53 function is sequence-specific transcriptional regulation of stress-response targets.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53.
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: MDM4/MDMX restrains p53 transactivation and forms a heterodimer with MDM2 to enhance p53 degradation.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:19749791
  review:
    summary: PMID:19749791 directly supports p53-dependent repression of SHP-1 transcription.
    action: ACCEPT
    reason: The paper reports endogenous or transfected wild-type p53 repressing SHP-1 expression through the SHP-1 promoter, supporting negative regulation of transcription.
    supported_by:
    - reference_id: PMID:19749791
      supporting_text: endogenous wtp53, activated by therapeutic agents, and transfected wtp53 repress expression of SHP-1
    - reference_id: PMID:19749791
      supporting_text: p53 repression of SHP-1 expression leads to trkA-Y674/Y675 phosphorylation
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:19749791
  review:
    summary: PMID:19749791 supports p53-dependent suppression of breast-cancer cell proliferation through SHP-1 repression and TrkA activation.
    action: ACCEPT
    reason: The original evidence directly reports suppressed proliferation when wild-type p53 represses SHP-1 and activates TrkA-dependent signaling.
    supported_by:
    - reference_id: PMID:19749791
      supporting_text: show suppressed cell proliferation
    - reference_id: PMID:19749791
      supporting_text: p53 repression of SHP-1 expression leads to trkA-Y674/Y675 phosphorylation and trkA-dependent suppression of breast-cancer cell proliferation.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IMP
  original_reference_id: PMID:19749791
  review:
    summary: PMID:19749791 directly supports p53-dependent repression of SHP-1 transcription.
    action: ACCEPT
    reason: The paper reports endogenous or transfected wild-type p53 repressing SHP-1 expression through the SHP-1 promoter, supporting negative regulation of transcription.
    supported_by:
    - reference_id: PMID:19749791
      supporting_text: endogenous wtp53, activated by therapeutic agents, and transfected wtp53 repress expression of SHP-1
    - reference_id: PMID:19749791
      supporting_text: p53 repression of SHP-1 expression leads to trkA-Y674/Y675 phosphorylation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11672522
  review:
    summary: protein binding is not a useful retained annotation for mouse p53 in this review, usually because it is too generic, weakly informative, or not directly tied to the curated p53 activity.
    action: REMOVE
    reason: The core Trp53 function is sequence-specific transcriptional regulation of stress-response programs; this term does not add a biologically informative or direct GO assertion.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: Mouse p53 is primarily a sequence-specific DNA-binding transcription factor; generic binding and broad phenotype terms do not capture the curated core activity.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: DNA binding is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005507
    label: copper ion binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Copper ion binding is not supported for mouse p53 by the cited evidence; UniProt documents Zn(2+) binding instead.
    action: MODIFY
    reason: Replace the unsupported copper-binding term with GO:0008270 zinc ion binding, the metal cofactor documented for p53.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
      supporting_text: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 1 zinc ion per subunit.
    proposed_replacement_terms:
    - id: GO:0008270
      label: zinc ion binding
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: nucleus is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: nucleolus is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: cytoplasm is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mitochondrion is a supported p53-associated context, interaction, localization, or downstream output, but it is not the core Trp53 molecular function.
    action: KEEP_AS_NON_CORE
    reason: Retain as non-core because Trp53/p53 is primarily a sequence-specific DNA-binding transcription factor; this term reflects regulatory context, stress response, localization, or a tissue-specific downstream consequence.
    supported_by:
    - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
      supporting_text: The p53 transcriptional program is tissue-, stress-, and context-dependent; many annotated responses are downstream or specialized outputs rather than the core molecular activity.
- term:
    id: GO:0006289
    label: nucleotide-excision repair
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: nucleotide-excision repair is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
- term:
    id: GO:0030308
    label: negative regulation of cell growth
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: negative regulation of cell growth is consistent with the curated mouse p53 biology as a stress-activated DNA-binding transcription factor, transcriptional regulator, or well-supported subcellular context.
    action: ACCEPT
    reason: The term fits the direct p53 activity or a well-established cellular context for that activity, supported by UniProt and the Falcon literature synthesis.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10329544
  title: Hepatitis C virus core protein interacts with a human DEAD box protein DDX3.
  findings: []
- id: PMID:10562313
  title: A proinflammatory cytokine inhibits p53 tumor suppressor activity.
  findings: []
- id: PMID:11181729
  title: The AKT3 potassium channel protein interacts with the AtPP2CA protein phosphatase 2C.
  findings: []
- id: PMID:11274052
  title: Naked cuticle targets dishevelled to antagonize Wnt signal transduction.
  findings: []
- id: PMID:11672522
  title: Negative control of p53 by Sir2alpha promotes cell survival under stress.
  findings: []
- id: PMID:11781573
  title: Design and application of a cytokine-receptor-based interaction trap.
  findings: []
- id: PMID:12667443
  title: p53 has a direct apoptogenic role at the mitochondria.
  findings: []
- id: PMID:15532030
  title: Coexpression of Brn-3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis.
  findings: []
- id: PMID:16151013
  title: PUMA couples the nuclear and cytoplasmic proapoptotic function of p53.
  findings: []
- id: PMID:16213212
  title: Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin.
  findings: []
- id: PMID:16407291
  title: 'Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53.'
  findings: []
- id: PMID:16480949
  title: The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein.
  findings: []
- id: PMID:16697373
  title: Interaction of nucleoside diphosphate kinase and catalases for stress and light responses in Neurospora crassa.
  findings: []
- id: PMID:17535810
  title: Functional similarity between the chloroplast translocon component, Tic40, and the human co-chaperone, Hsp70-interacting protein (Hip).
  findings: []
- id: PMID:17936560
  title: Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation.
  findings: []
- id: PMID:18025262
  title: Interaction between transcription factor, basal transcription factor 3, and the NH2-terminal domain of human estrogen receptor alpha.
  findings: []
- id: PMID:18303029
  title: BAF60a interacts with p53 to recruit the SWI/SNF complex.
  findings: []
- id: PMID:18359851
  title: Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2.
  findings: []
- id: PMID:18448518
  title: The nucleocapsid protein of severe acute respiratory syndrome coronavirus inhibits cell cytokinesis and proliferation by interacting with translation elongation factor 1alpha.
  findings: []
- id: PMID:18695251
  title: AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53.
  findings: []
- id: PMID:19011633
  title: Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin.
  findings: []
- id: PMID:19556538
  title: Trim24 targets endogenous p53 for degradation.
  findings: []
- id: PMID:19749791
  title: Repression of SHP-1 expression by p53 leads to trkA tyrosine phosphorylation and suppression of breast cancer cell proliferation.
  findings: []
- id: PMID:20599664
  title: A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein.
  findings: []
- id: PMID:20621096
  title: Deletion of Swm2p selectively impairs trimethylation of snRNAs by trimethylguanosine synthase (Tgs1p).
  findings: []
- id: PMID:20697359
  title: 'Regulation of MDM4 (MDMX) function by p76(MDM2): a new facet in the control of p53 activity.'
  findings: []
- id: PMID:20708612
  title: DJ-1, an oncogene and causative gene for familial Parkinson's disease, is essential for SV40 transformation in mouse fibroblasts through up-regulation of c-Myc.
  findings: []
- id: PMID:20818388
  title: Puma is required for p53-induced depletion of adult stem cells.
  findings: []
- id: PMID:20832751
  title: An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction.
  findings: []
- id: PMID:21057544
  title: p85α mediates p53 K370 acetylation by p300 and regulates its promoter-specific transactivity in the cellular UVB response.
  findings: []
- id: PMID:21122074
  title: Interaction of Sesbania mosaic virus movement protein with the coat protein--implications for viral spread.
  findings: []
- id: PMID:21670284
  title: Near-UV cyanobacteriochrome signaling system elicits negative phototaxis in the cyanobacterium Synechocystis sp. PCC 6803.
  findings: []
- id: PMID:21741598
  title: A Pin1/mutant p53 axis promotes aggressiveness in breast cancer.
  findings: []
- id: PMID:21857681
  title: A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1.
  findings: []
- id: PMID:21909133
  title: Manganese superoxide dismutase is a mitochondrial fidelity protein that protects Polγ against UV-induced inactivation.
  findings: []
- id: PMID:22056770
  title: Structural basis for the molecular evolution of SRP-GTPase activation by protein.
  findings: []
- id: PMID:22262176
  title: Ribosomal stress induces L11- and p53-dependent apoptosis in mouse pluripotent stem cells.
  findings: []
- id: PMID:22726440
  title: p53 opens the mitochondrial permeability transition pore to trigger necrosis.
  findings: []
- id: PMID:23123091
  title: Involvement of PTEN in TPA-mediated p53-activation in mouse skin epidermal JB6 cells.
  findings: []
- id: PMID:23629966
  title: Deacetylation of p53 induces autophagy by suppressing Bmf expression.
  findings: []
- id: PMID:23980194
  title: E258K HCM-causing mutation in cardiac MyBP-C reduces contractile force and accelerates twitch kinetics by disrupting the cMyBP-C and myosin S2 interaction.
  findings: []
- id: PMID:24051492
  title: p53 regulates Period2 expression and the circadian clock.
  findings: []
- id: PMID:24116158
  title: The nuclear envelope protein, LAP1B, is a novel protein phosphatase 1 substrate.
  findings: []
- id: PMID:24240685
  title: FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage.
  findings: []
- id: PMID:25117711
  title: Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and development, but essential in response to DNA damage.
  findings: []
- id: PMID:26960425
  title: Yeast Two-Hybrid Screening for Proteins that Interact with the Extracellular Domain of Amyloid Precursor Protein.
  findings: []
- id: PMID:27258785
  title: The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873.
  findings: []
- id: PMID:28536627
  title: The identification of human aldo-keto reductase AKR7A2 as a novel cytoglobin-binding partner.
  findings: []
- id: PMID:30089260
  title: p53 Regulates the Expression of LRP1 and Apoptosis through a Stress Intensity-Dependent MicroRNA Feedback Loop.
  findings: []
- id: PMID:37025149
  title: Arabidopsis LFR, a SWI/SNF complex component, interacts with ICE1 and activates ICE1 and CBF3 expression in cold acclimation.
  findings: []
- id: PMID:9194565
  title: Binding and modulation of p53 by p300/CBP coactivators.
  findings: []
- id: Reactome:R-MMU-9816449
  title: Dppa2 and Dppa4 bind the Dux gene cluster
  findings: []
- id: file:mouse/Trp53/Trp53-uniprot.txt
  title: UniProt record for mouse Trp53
  findings:
  - statement: Trp53 encodes p53, a multifunctional transcription factor that induces cell cycle arrest, DNA repair, or apoptosis after binding target DNA sequences.
    supporting_text: Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
- id: file:mouse/Trp53/Trp53-deep-research-falcon.md
  title: Falcon deep research report on mouse Trp53
  findings:
  - statement: Falcon synthesis verifies mouse Trp53/p53 as a sequence-specific DNA-binding transcription factor with tissue- and stress-specific outputs.
    supporting_text: Mouse Tp53 (Trp53; UniProt P02340) encodes p53, a stress-activated, sequence-specific DNA-binding transcription factor.
core_functions:
- description: Trp53/p53 acts primarily as a nuclear sequence-specific DNA-binding transcription factor that binds p53 response elements and regulates RNA polymerase II target genes controlling DNA damage responses, cell-cycle arrest, apoptosis, and senescence.
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0030330
    label: DNA damage response, signal transduction by p53 class mediator
  - id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  - id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  - id: GO:0072332
    label: intrinsic apoptotic signaling pathway by p53 class mediator
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0000785
    label: chromatin
  supported_by:
  - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
    supporting_text: p53 is primarily a sequence-specific DNA-binding transcription factor that regulates stress-responsive gene expression programs.
- description: p53 oligomerization supports DNA binding and transcriptional target selection; the active transcription factor binds DNA as a homotetramer and integrates stress-dependent post-translational regulation with cell fate outputs.
  molecular_function:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  directly_involved_in:
  - id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
  - id: GO:2000774
    label: positive regulation of cellular senescence
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005654
    label: nucleoplasm
  supported_by:
  - reference_id: file:mouse/Trp53/Trp53-uniprot.txt
    supporting_text: Forms homodimers and homotetramers. Binds DNA as a homotetramer.
  - reference_id: file:mouse/Trp53/Trp53-deep-research-falcon.md
    supporting_text: 'DNA binding is coupled to oligomerization: p53 transitions ... to a functional tetramer.'
proposed_new_terms: []
suggested_questions:
- question: Which mouse tissues use conserved p53 target programs versus tissue-specific target genes after comparable stress inputs?
- question: Which mitochondrial and cytoplasmic p53 annotations should be retained as direct activities rather than stress-context localizations?
suggested_experiments:
- description: Use Trp53 response-reporter mouse cells with matched DNA damage, hypoxia, and metabolic stress treatments to map direct p53 binding, target transcription, and cell fate outputs by tissue.
- description: Compare wild-type and DNA-binding-defective Trp53 alleles in primary mouse cells to separate direct transcriptional effects from non-transcriptional mitochondrial apoptosis functions.

Trp53

Gene Description

Existing Annotations Review

Core Functions

Trp53/p53 acts primarily as a nuclear sequence-specific DNA-binding transcription factor that binds p53 response elements and regulates RNA polymerase II target genes controlling DNA damage responses, cell-cycle arrest, apoptosis, and senescence.

p53 oligomerization supports DNA binding and transcriptional target selection; the active transcription factor binds DNA as a homotetramer and integrates stress-dependent post-translational regulation with cell fate outputs.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Deep Research Bioreason

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Deep Research Bioreason Rl

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Comprehensive Functional Annotation Report: Mouse Tp53 / Trp53 (UniProt P02340)

0) Target verification (critical disambiguation)

1) Key concepts and definitions (current understanding)

1.1 Core molecular function

1.2 Domain architecture (structure-function definitions)

1.3 Canonical pathway logic (definitions)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 Tissue specificity and “spatiotemporal” p53 programs in vivo (2023)

2.2 Multi-layer regulation and PTM-centric models of p53 control (2024)

2.3 New mouse tools enabling in situ p53 cell-fate tracking (2024)

3) Functional annotation: biological processes, pathways, and cellular localization

3.1 Subcellular localization (where p53 acts)

3.2 Canonical stress→p53→cell fate pathways

3.3 Metabolism and ferroptosis (expanding functional scope)

4) Expert opinions and authoritative analysis (what leading reviews emphasize)

4.1 p53 as “undruggable” but increasingly actionable

4.2 Context-dependence is central to interpreting p53 function in vivo

5) Mouse genetic evidence, statistics, and quantitative findings (recently summarized)

5.1 Essentiality of Mdm2/Mdm4 restraint of p53 (causal genetics)

5.2 Quantitative transcriptional induction of p53 targets in vivo

5.3 PTM knock-in mouse models connect molecular regulation to tumor suppression

5.4 New mouse “real-world” implementations: reporters for fate decisions

6) Current applications and real-world implementations

6.1 In vivo biology and single-cell fate tracking

6.2 Pharmacologic activation of p53 signaling (preclinical and translational)

7) Visual evidence (key figure/table)

Evidence map (compact)

8) Summary functional annotation (mouse Tp53 / p53)

Citations

Bioreason Rl Review

BioReason-Pro RL Review: Trp53 (mouse)

Functional Summary Review

Notes on thinking trace

📄 View Raw YAML