Tp53 (rat; UniProt P10361) encodes cellular tumor antigen p53, a conserved p53-family, sequence-specific DNA-binding transcription factor that acts as the central node of the cellular stress response and as a tumor suppressor ("guardian of the genome"). p53 has a modular architecture (N-terminal transactivation domains, proline-rich region, central sequence-specific DNA-binding domain, and an oligomerization/tetramerization domain); the active protein assembles into homotetramers that bind p53 response elements in target gene promoters/enhancers. In response to diverse stresses (notably DNA damage, but also oxidative stress, hypoxia, ribosomal/nucleolar stress and oncogene activation), p53 is stabilized β chiefly by escape from MDM2/MDM4-mediated ubiquitination β and drives transcriptional programs governing cell-cycle arrest (via CDKN1A/p21), apoptosis (via PUMA, BAX, NOXA), DNA repair and senescence. p53 also induces MDM2, forming an autoregulatory negative-feedback loop. It functions predominantly as a nuclear transcription factor but also has transcription-independent cytoplasmic/mitochondrial pro-apoptotic and pro-necrotic actions, the latter via opening of the mitochondrial permeability transition pore under oxidative stress. Its core conserved activity is sequence-specific DNA-binding transcription factor activity coupled to the DNA-damage and stress response; its many tissue- and stimulus-specific effects (on metabolism, autophagy, senescence and cell death in particular cell types) arise largely downstream of this activity rather than from additional distinct molecular functions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: This is the core, defining molecular function of p53. As a sequence-specific DNA-binding transcription factor, p53 binds p53 response elements and modulates RNA polymerase II transcription of stress-response target genes. Phylogenetic (IBA) inference is sound and corroborated by the deep research. Reason: Core molecular function of p53, universally applicable across p53-family orthologs and strongly supported by literature. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Tp53 encodes p53, a sequence-specific DNA-binding transcription factor** that acts as a central stress-response node and tumor suppressor file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IBA GO_REF:0000033 | ACCEPT | Summary: p53 is the canonical mediator of the intrinsic (mitochondrial) apoptotic pathway following DNA damage, transactivating PUMA, BAX and NOXA. This is a core p53 process and is the most specific GO term capturing p53-dependent DNA-damage apoptosis. Reason: Core, p53-specific biological process; well-supported phylogenetic inference. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0042981 regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: p53 regulates apoptosis, but this generic term is subsumed by the far more specific and informative p53-mediated intrinsic apoptosis terms (GO:0042771, GO:0072332, GO:2001242). Retained as non-core because it is correct but not the most informative representation. Reason: Correct but generic; the p53-specific apoptosis terms better capture the core function. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:1990841 promoter-specific chromatin binding | IBA GO_REF:0000033 | ACCEPT | Summary: p53 binds promoter/enhancer chromatin at response elements as part of its transcription factor function. Consistent with the core DNA-binding activity. Reason: Supports the core sequence-specific DNA/chromatin-binding function. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: p53 functions predominantly as a nuclear transcription factor where stabilized tetramers bind DNA response elements. This is the core site of action. Reason: Core localization for the transcription factor function. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Nuclear:** stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: p53 transactivates target genes (e.g. CDKN1A/p21, MDM2, pro-apoptotic genes) via RNA polymerase II, a core aspect of its transcriptional activator function. Reason: Core function; p53 is a sequence-specific transcriptional activator. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: p53 is located at chromatin where it binds response elements. Consistent with its DNA-binding transcription factor role. Reason: Core localization for the DNA-binding function. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: p53 binds sequence-specific cis-regulatory regions (p53 response elements) of Pol II target genes. This is a precise statement of the core DNA-binding activity. Reason: Core molecular function; precise DNA-binding specificity term. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic parent of the more specific GO:0000978 sequence-specific cis-regulatory binding already annotated. Correct but redundant/less informative. Reason: Correct but generic; superseded by the more specific DNA-binding terms. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic DNA binding; subsumed by the specific sequence-specific DNA binding (GO:0043565) and cis-regulatory binding terms that capture p53's actual specificity. Reason: Correct but uninformatively generic; more specific terms preferred. Supporting Evidence: UniProtKB:P10361 Binds DNA as a homotetramer. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Parent of the Pol II-specific term GO:0000981 already annotated as core. Correct but the Pol II-specific child is more informative. Reason: Generic parent of the core MF term GO:0000981. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Redundant nucleus annotation (also asserted by IBA). Core localization. Reason: Core localization; duplicate of the IBA nucleus annotation. Supporting Evidence: UniProtKB:P10361 Cytoplasm {ECO:0000250|UniProtKB:P04637}. Nucleus {ECO:0000250|UniProtKB:P04637}. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: p53 is also present in the cytoplasm, where a stress-stabilized pool can engage mitochondria for transcription-independent apoptosis. Non-core relative to the primary nuclear TF function. Reason: Real but secondary localization; the core function is nuclear. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Mitochondrial matrix from the UniProt subcellular-location mapping (SL-0170). Under oxidative stress or ischemia p53 accumulates in the mitochondrial matrix and binds cyclophilin D (PPIF) to open the permeability transition pore, triggering necrosis. Reason: Changed from MODIFY (to mitochondrial outer membrane) on re-review. The earlier view that mitochondrial p53 acts only at the outer membrane is contradicted by direct evidence of matrix accumulation and matrix CypD engagement (PMID:22726440) and CHCHD4-dependent import into mitochondria (PMID:24101517). Outer-membrane (BCL-2-family) and matrix pools both exist; the matrix location is correct but stress-induced and transcription-independent, hence non-core. Supporting Evidence: PMID:22726440 In response to oxidative stress and ischemia, p53 protein accumulates in the mitochondrial matrix and triggers PTP opening, mPT and necrosis by physical interaction with the critical PTP regulator CypD. UniProtKB:P10361 Endoplasmic reticulum {ECO:0000250|UniProtKB:P04637}. Mitochondrion matrix |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: ER localization is not a recognized site of p53 function; this IEA subcellular-location mapping likely reflects transient/contextual detection rather than a functional compartment for p53. Reason: Not a recognized functional compartment for p53; imprecise IEA mapping. Supporting Evidence: PMID:17170702 Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centrosomal p53 has been reported in the context of centrosome-duplication surveillance, but it is a peripheral, non-core localization relative to the nuclear TF function. Reason: Peripheral localization linked to centrosome surveillance; not core. Supporting Evidence: UniProtKB:P10361 Cytoplasm, cytoskeleton, microtubule organizing center, centrosome |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic transcription regulation; subsumed by the specific Pol II positive/negative regulation terms already annotated. Reason: Correct but generic parent of the more specific Pol II regulation terms. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0006915 apoptotic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: p53 is a master regulator/inducer of apoptosis. As a bare process term it is generic; the regulatory and p53-specific intrinsic-apoptosis terms are more informative, but apoptosis is genuinely central to p53 biology. Reason: Generic; the p53-mediated intrinsic apoptosis terms capture the core role. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p53 is activated by and responds to oxidative stress as part of its stress-sensing function. A genuine but downstream/contextual stress response. Reason: One of many specific stress stimuli that activate the core stress response. Supporting Evidence: UniProtKB:P10361 Translocates to mitochondria upon oxidative stress. UniProtKB:P10361 In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: A specific stimulus that can activate p53; downstream/contextual rather than a core molecular function. Reason: Specific stress stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0009411 response to UV | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: UV is a classic DNA-damaging stimulus that activates p53. A specific instance of the DNA-damage response; non-core as a standalone term. Reason: Specific DNA-damage stimulus; subsumed by the core DNA-damage response. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0010165 response to X-ray | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Ionizing radiation (X-ray) activates the p53 DNA-damage response. Specific stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0016605 PML body | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: p53 localizes to PML nuclear bodies, which modulate its acetylation and activation. A real but specialized sub-nuclear localization; non-core. Reason: Specialized sub-nuclear localization relevant to p53 regulation; non-core. Supporting Evidence: UniProtKB:P10361 Recruited into PML bodies together with CHEK2. |
| GO:0031625 ubiquitin protein ligase binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p53 binds the E3 ubiquitin ligase MDM2 (and others), central to its regulation. A meaningful interaction underlying the MDM2 feedback loop, but not the core molecular activity. Reason: Captures MDM2/E3 ligase interaction central to p53 turnover; regulatory, not the core MF. Supporting Evidence: UniProtKB:P10361 Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. |
| GO:0051053 negative regulation of DNA metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Very generic; p53 can negatively regulate DNA replication/synthesis under stress, but this term is uninformative relative to specific checkpoint/repair terms. Reason: Overly generic ARBA-derived term; more specific checkpoint terms preferred. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0051262 protein tetramerization | IEA GO_REF:0000002 | ACCEPT | Summary: Active p53 assembles into homotetramers via its oligomerization domain; tetramerization is required for efficient DNA binding and full transactivation. A genuine, mechanistically important molecular feature. Reason: Tetramerization is an experimentally established, functionally required property of p53. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md activated p53 forms tetramers; tetramerization is required for efficient DNA binding and full transactivation |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Hypoxia is one of the stresses that activates p53. A specific stimulus response; non-core. Reason: Specific stress stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0097190 apoptotic signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Generic apoptotic signaling; subsumed by the p53-specific intrinsic apoptosis terms. Correct but not most informative. Reason: Generic; p53-specific intrinsic apoptosis terms are more informative. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0097371 MDM2/MDM4 family protein binding | IEA GO_REF:0000117 | ACCEPT | Summary: p53 binds MDM2/MDM4, the principal negative regulators that control its stability and the autoregulatory feedback loop. A core regulatory interaction of the pathway. Reason: Direct, well-established interaction central to p53 regulation. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md MDM2 ubiquitinylates p53, inhibiting transactivation and promoting nuclear export and degradation; stress disrupts this interaction, stabilizing p53 |
| GO:2001242 regulation of intrinsic apoptotic signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p53 regulates the intrinsic apoptotic pathway. Consistent with core p53 apoptosis function, though the positive-regulation child term is more specific. Reason: Correct; subsumed by the more specific positive-regulation term GO:2001244. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Reflects p53 self-association into homo-oligomers/tetramers. Captured more precisely by protein tetramerization (GO:0051262). Generic binding term. Reason: Generic restatement of homotetramerization; protein tetramerization is preferred. Supporting Evidence: UniProtKB:P10361 Forms homodimers and homotetramers (By similarity). |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | ACCEPT | Summary: p53 acts in the nucleoplasm as a transcription factor. Consistent with the core nuclear localization. Reason: Core localization consistent with nuclear TF function. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0005829 cytosol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A cytosolic p53 pool exists and contributes to transcription-independent apoptosis. Non-core relative to nuclear function. Reason: Secondary cytosolic localization; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:1990841 promoter-specific chromatin binding | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the IBA promoter-specific chromatin binding annotation. Supports the core DNA-binding function. Reason: Supports core DNA/chromatin-binding function; duplicate of IBA call. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0010628 positive regulation of gene expression | IGI PMID:23164821 Clusterin regulates Ξ²-amyloid toxicity via Dickkopf-1-driven... | MARK AS OVER ANNOTATED | Summary: Very generic positive regulation of gene expression. p53 does activate gene expression, but the specific Pol II transactivation terms are far more informative. The cited paper concerns clusterin/Dickkopf-1/Wnt in amyloid toxicity, a peripheral context. Reason: Generic; subsumed by specific Pol II transactivation terms. Supporting Evidence: PMID:23164821 resulting in the p53-dependent induction of DKK1. |
| GO:0001223 transcription coactivator binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 binds transcriptional coactivators (e.g. p300/CBP) to drive transactivation. A genuine MF supporting the core transcriptional activator function. Reason: Supports transactivation via coactivator recruitment; ancillary to the core DNA-binding MF. Supporting Evidence: UniProtKB:P10361 Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) nucleus annotation. Core localization. Reason: Core localization; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0140693 molecular condensate scaffold activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: p53 has been reported to undergo phase separation in vitro, but condensate scaffold activity as a physiological function for rat p53 is not well established; ISS transfer is speculative. Reason: Speculative; condensate scaffolding is not an established core function. Supporting Evidence: UniProtKB:P10361 The N-terminal and C-terminal disordered regions undergo liquid-liquid phase separation (LLPS) following homotetramerization and activation. |
| GO:0140693 molecular condensate scaffold activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the speculative condensate scaffold activity annotation. Reason: Speculative; not an established core function. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P04637 Β· human TP53 SOURCE WEAK OR INFERRED The human TP53 condensate-scaffold annotations are recent IDAs from in vitro phase-separation studies (e.g. PMID:35618207, PMID:36634798); too speculative to transfer as a rat function. Supporting Evidence: UniProtKB:P10361 The N-terminal and C-terminal disordered regions undergo liquid-liquid phase separation (LLPS) following homotetramerization and activation. |
| GO:0032211 negative regulation of telomere maintenance via telomerase | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 can repress TERT and limit telomerase, linked to senescence. A specific downstream transcriptional-repression output; non-core. Reason: Specific downstream repression output; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core positive-regulation-of-Pol-II-transcription annotation. Reason: Core function; duplicate of IBA call. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 transactivates specific miRNAs (e.g. miR-34 family). A specific downstream transcriptional output; non-core. Reason: Specific transcriptional output; non-core. Supporting Evidence: PMID:21522133 Functional analysis revealed that this transcriptional activation of miR-29 is triggered in response to DNA damage and occurs in a p53-dependent manner |
| GO:0003700 DNA-binding transcription factor activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the generic DNA-binding TF activity; parent of the core Pol II-specific term. Reason: Generic parent of core MF term GO:0000981. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0006357 regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic parent of the specific positive/negative Pol II regulation terms already annotated. Reason: Generic parent term; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core sequence-specific cis-regulatory DNA-binding annotation. Reason: Core DNA-binding specificity; duplicate of IBA call. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:0097190 apoptotic signaling pathway | IMP PMID:17998337 p53 initiates apoptosis by transcriptionally targeting the a... | KEEP AS NON CORE | Summary: Experimental (IMP) support that p53 initiates apoptotic signaling by transactivating a target (ARC). Genuine, though the generic term is subsumed by p53-specific intrinsic apoptosis terms. Reason: Generic apoptotic signaling; p53-specific intrinsic apoptosis terms preferred. Supporting Evidence: PMID:17998337 Here, we report that p53 can transcriptionally target the antiapoptotic protein, apoptosis repressor with caspase recruitment domain (ARC). |
| GO:0005515 protein binding | IPI PMID:11278372 Stabilization and activation of p53 by the coactivator prote... | MODIFY | Summary: IPI for p53 binding the TFIID subunit TAF(II)31 (TAF9), described in the paper as a coactivator. TAF(II)31 binds the p53 N-terminus, blocks MDM2-mediated ubiquitination and enhances p53 transactivation. Reason: Generic protein binding is uninformative. The cited paper characterizes the partner as a transcriptional coactivator that binds the p53 transactivation region, which is captured by transcription coactivator binding (already carried by ISO). Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:11278372 The coactivator protein TAF(II)31 binds to p53 at the amino-terminal region that is also required for interaction with mdm2. PMID:11278372 TAF(II)31-mediated p53 stabilization results in activation of p53-mediated transcriptional activity and leads to p53-dependent growth arrest in fibroblasts. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Generic positive regulation of gene expression; subsumed by specific Pol II transactivation terms. Reason: Generic; specific Pol II transactivation terms preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor evidence (IDA/IMP, e.g. PMID:20332243, PMID:19160485) is for specific Pol II transactivation events; the generic parent term adds nothing. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0045815 transcription initiation-coupled chromatin remodeling | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 recruits chromatin remodelers/coactivators during transactivation. A mechanistic detail of transactivation; non-core. Reason: Mechanistic detail of p53 transactivation; non-core. Supporting Evidence: UniProtKB:P10361 Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. |
| GO:0016605 PML body | IDA PMID:17289031 Subcellular localization of Daxx determines its opposing fun... | KEEP AS NON CORE | Summary: Direct (IDA) localization to PML nuclear bodies. A real but specialized sub-nuclear localization tied to p53 acetylation/activation; non-core. Reason: Specialized sub-nuclear localization; non-core. Supporting Evidence: UniProtKB:P10361 Recruited into PML bodies together with CHEK2. |
| GO:0071456 cellular response to hypoxia | IEP PMID:17289031 Subcellular localization of Daxx determines its opposing fun... | KEEP AS NON CORE | Summary: Expression-pattern (IEP) evidence linking p53 to hypoxic/ischemic response. A specific stimulus response; non-core. Reason: Specific stress stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0044325 transmembrane transporter binding | IPI PMID:27013579 Suppressing activity of tributyrin on hepatocarcinogenesis i... | MARK AS OVER ANNOTATED | Summary: The cited study concerns p53-CRM1 interaction and nucleocytoplasmic compartmentalization; CRM1 (XPO1) is an exportin, not a transmembrane transporter. The mapping to transmembrane transporter binding appears mislabeled. Reason: The GO term is mislabeled for this interaction. CRM1/XPO1 is a soluble nuclear export receptor (karyopherin/exportin), not a transmembrane transporter, so the underlying p53-CRM1 nuclear-export interaction (PMID:27013579) does not map to transmembrane transporter binding. Supporting Evidence: PMID:27013579 Mechanistically, the increase in the level of nuclear p53 protein was associated with a substantially reduced binding interaction between CRM1 and p53. |
| GO:0071401 cellular response to triglyceride | IEP PMID:27013579 Suppressing activity of tributyrin on hepatocarcinogenesis i... | KEEP AS NON CORE | Summary: Highly specific contextual stimulus (tributyrin/triglyceride in a hepatocarcinogenesis model). Peripheral to p53's core function. Reason: Narrow contextual stimulus response; non-core. Supporting Evidence: PMID:27013579 The cancer-inhibitory effect of tributyrin was linked to the suppression of sustained cell proliferation and induction of apoptotic cell death driven by an activation of the p53 apoptotic signaling pathway. |
| GO:0000785 chromatin | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) chromatin localization. Consistent with core DNA-binding. Reason: Core localization for DNA-binding function; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:2000774 positive regulation of cellular senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 is a master inducer of cellular senescence (via p21 and other effectors). A genuine core-adjacent output of the p53 stress response. Reason: Senescence induction is a canonical p53 output; retained as non-core (one of the major cell-fate programs, captured at the core level via the stress response). Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 coordinates programs that enforce durable arrest and facilitate genomic maintenance |
| GO:0071889 14-3-3 protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 interacts with 14-3-3 proteins, modulating its stability/activity. A specific regulatory interaction; non-core. Reason: Specific regulatory protein interaction; non-core. Supporting Evidence: UniProtKB:P10361 Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. |
| GO:0140677 molecular function activator activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Very generic 'activator activity' term. p53 activates transcription, but this MF term is uninformative relative to its DNA-binding TF activity. Reason: Generic/uninformative MF; specific TF terms preferred. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor rows (EXP/IPI, e.g. PMID:7559631) describe specific activation events; the root-level activator-activity term is uninformative for the rat gene. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0090398 cellular senescence | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cellular senescence is a canonical p53-controlled cell-fate program. A genuine, important downstream output of the p53 stress response. Reason: Major p53 cell-fate program; captured at the core level via the stress response, retained as non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0090398 cellular senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) cellular senescence annotation. Reason: Duplicate; major p53 cell-fate program, non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0007283 spermatogenesis | IMP PMID:28834365 Spontaneous testicular atrophy occurs despite normal spermat... | KEEP AS NON CORE | Summary: A Tp53-knockout rat shows testicular atrophy despite normal spermatogonial proliferation. This is a pleiotropic developmental/tissue phenotype, not a core molecular function of p53. Reason: Pleiotropic tissue-level phenotype; non-core. Supporting Evidence: PMID:28834365 p53 knockout rats exhibited variable levels of testicular atrophy, including significantly decreased testis weights, atrophic seminiferous tubules, decreased seminiferous tubule diameter, and elevated spermatocyte TUNEL labeling rates, indicating a dysfunction in spermatogenesis. |
| GO:0010165 response to X-ray | IMP PMID:28834365 Spontaneous testicular atrophy occurs despite normal spermat... | KEEP AS NON CORE | Summary: Experimental support that p53 mediates the X-ray (ionizing radiation) response in rat tissue. A specific instance of the DNA-damage response; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: PMID:28834365 p53 knockout rats exhibited no germ cell apoptotic response beyond their unirradiated phenotype, while germ cell death in wild-type rat testes was elevated to a level similar to the unexposed p53 knockout rats. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:28834365 Spontaneous testicular atrophy occurs despite normal spermat... | KEEP AS NON CORE | Summary: Context-dependent anti-apoptotic effect reported in the Tp53-knockout rat testis study. p53 is predominantly pro-apoptotic; this opposite-direction effect is context-specific and non-core. Reason: Context-specific anti-apoptotic effect; non-core (p53's core apoptotic role is pro-apoptotic). Supporting Evidence: PMID:28834365 p53 knockout rats exhibited no germ cell apoptotic response beyond their unirradiated phenotype, while germ cell death in wild-type rat testes was elevated to a level similar to the unexposed p53 knockout rats. |
| GO:0051726 regulation of cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 regulates the cell cycle via p21-mediated arrest. Core-adjacent; the specific checkpoint terms are more informative but this captures a canonical output. Reason: Generic; specific checkpoint/arrest terms preferred. Canonical p53 output. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: p53 represses a subset of target genes (e.g. via repression of survival/cell-cycle genes). Transcriptional repression is a genuine part of the p53 program. Reason: p53 acts as both activator and repressor of Pol II transcription; this is part of the core transcriptional regulator function. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: Closely related to the core sequence-specific cis-regulatory DNA-binding function (GO:0000978). Supports the core DNA-binding activity. Reason: Core DNA-binding specificity. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: p53 has sequence-specific repressor activity for a subset of targets. Part of the core transcription factor function (dual activator/repressor). Reason: Core MF; p53 acts as a sequence-specific repressor for some targets. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. PMID:10329733 This activation of the Bcl-2 promoter by Brn-3a is strongly inhibited by the p53 anti-oncogene protein. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:30514107 CELF1/p53 axis: a sustained antiproliferative signal leading... | KEEP AS NON CORE | Summary: Experimental support (CELF1/p53 axis, villus atrophy) that p53 suppresses proliferation. A canonical tumor-suppressive output via cell-cycle arrest. Reason: Canonical antiproliferative output; captured at the core level via cell-cycle arrest/stress response. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0051726 regulation of cell cycle | IMP PMID:30514107 CELF1/p53 axis: a sustained antiproliferative signal leading... | KEEP AS NON CORE | Summary: Experimental (IMP) support for p53 regulation of the cell cycle. Canonical p53 output; generic term subsumed by specific checkpoint terms. Reason: Generic; canonical output, specific checkpoint terms preferred. Supporting Evidence: PMID:30514107 Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). |
| GO:1903451 negative regulation of G1 to G0 transition | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Specific cell-cycle/quiescence regulatory term. A downstream detail of p53's cell-cycle control; non-core. Reason: Specific cell-cycle regulatory detail; non-core. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:1902749 regulation of cell cycle G2/M phase transition | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 contributes to the G2/M checkpoint. A specific aspect of cell-cycle arrest; non-core relative to the overall arrest program. Reason: Specific checkpoint detail; non-core. Supporting Evidence: UniProtKB:P10361 Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A stress-stabilized p53 pool relocalizes to mitochondria for transcription-independent apoptosis. Real but secondary localization; non-core. Reason: Secondary localization supporting transcription-independent apoptosis; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0036310 ATP-dependent DNA/DNA annealing activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: An in-vitro reannealing/strand-transfer activity reported for the p53 C-terminus. This is an in-vitro biochemical curiosity, not an established in-vivo function, and ISS transfer is weakly supported. Reason: In-vitro-only activity not established as a physiological function; weak ISS support. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0036310 ATP-dependent DNA/DNA annealing activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the in-vitro DNA annealing activity. Reason: In-vitro-only activity; not an established physiological function. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P04637 Β· human TP53 SOURCE WEAK OR INFERRED The human donor evidence is a single early in vitro biochemical IDA (PMID:8183576) with no established physiological role. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0140296 general transcription initiation factor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 contacts general transcription machinery (e.g. TFIID/TBP) during transactivation. A mechanistic interaction supporting the core TF function. Reason: Mechanistic interaction supporting transactivation; ancillary to core MF. Supporting Evidence: UniProtKB:P10361 Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: The specific sequence-specific transcriptional activator activity of p53 for Pol II targets. Together with the repressor activity, this constitutes the core MF. Reason: Core molecular function; p53 is a sequence-specific Pol II transcriptional activator. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Context-dependent anti-apoptotic role transferred by orthology. p53 is predominantly pro-apoptotic; the opposite-direction effect is context-specific and non-core. Reason: Context-specific; p53's core apoptotic role is pro-apoptotic. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0045899 positive regulation of RNA polymerase II transcription preinitiation complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A mechanistic detail of p53-driven transactivation (promoting PIC assembly). Supports the core activator function; non-core as a standalone term. Reason: Mechanistic transactivation detail; non-core. Supporting Evidence: UniProtKB:P10361 Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex. |
| GO:0033209 tumor necrosis factor-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 intersects with TNF/death-receptor signaling in some contexts. A peripheral cross-talk; non-core. Reason: Peripheral signaling cross-talk; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0001046 core promoter sequence-specific DNA binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 binds sequence-specific DNA; whether it specifically binds the core promoter (vs distal/proximal response elements) is debatable. Related to the core DNA-binding function but the specific 'core promoter' qualifier may be over-specific. Reason: Related to core DNA-binding; the core-promoter specificity is uncertain. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:0005813 centrosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Centrosomal localization linked to centrosome-duplication surveillance. Peripheral; non-core. Reason: Peripheral localization; non-core. Supporting Evidence: UniProtKB:P10361 Cytoplasm, cytoskeleton, microtubule organizing center, centrosome |
| GO:0005813 centrosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) centrosome localization. Reason: Peripheral localization; non-core; duplicate. Supporting Evidence: UniProtKB:P10361 Cytoplasm, cytoskeleton, microtubule organizing center, centrosome |
| GO:0043065 positive regulation of apoptotic process | ISS GO_REF:0000024 | ACCEPT | Summary: p53 is a master positive regulator of apoptosis, transactivating PUMA, BAX and NOXA. This is a canonical core p53 output. Reason: Canonical, well-established pro-apoptotic role; core p53 output. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:10329733 p53 suppresses the activation of the Bcl-2 promoter by the B... | KEEP AS NON CORE | Summary: Direct interaction (IPI) with another Pol II transcription factor (Brn-3a) to modulate the Bcl-2 promoter. A specific cofactor/TF interaction; non-core. Reason: Specific TF-TF interaction; ancillary to the core MF. Supporting Evidence: PMID:10329733 Moreover, Brn-3a and p53 have been shown to bind to adjacent sites in the p2 promoter and to directly interact with one another, both in vitro and in vivo, with this interaction being mediated by the POU domain of Brn-3a and the DNA binding domain of p53. |
| GO:0090575 RNA polymerase II transcription regulator complex | IDA PMID:10329733 p53 suppresses the activation of the Bcl-2 promoter by the B... | ACCEPT | Summary: p53 is part of Pol II transcription regulator complexes at target promoters. Consistent with the core transcription factor function. Reason: Consistent with core TF function; p53 acts within Pol II regulatory complexes. Supporting Evidence: PMID:10329733 Moreover, Brn-3a and p53 have been shown to bind to adjacent sites in the p2 promoter and to directly interact with one another, both in vitro and in vivo, with this interaction being mediated by the POU domain of Brn-3a and the DNA binding domain of p53. |
| GO:0002244 hematopoietic progenitor cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Pleiotropic tissue/developmental role transferred by orthology. Non-core. Reason: Pleiotropic developmental role; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0060218 hematopoietic stem cell differentiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Pleiotropic developmental role transferred by orthology. Non-core. Reason: Pleiotropic developmental role; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0048539 bone marrow development | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Pleiotropic tissue/developmental role transferred by orthology. Non-core. Reason: Pleiotropic developmental role; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: p53 positively regulates the intrinsic apoptotic pathway. A core p53 apoptosis term, specific to the p53-driven mitochondrial program. Reason: Core p53 apoptosis output; specific and informative. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | IMP PMID:27031958 Nupr1/Chop signal axis is involved in mitochondrion-related ... | ACCEPT | Summary: Experimental (IMP) support for p53 positively regulating intrinsic apoptosis (Nupr1/Chop axis, mitochondrial endothelial apoptosis). Core p53 apoptosis output. Reason: Core p53 apoptosis output; experimentally supported. Supporting Evidence: PMID:27031958 Nupr1/Chop/P53 axis is involved in classical mitochondrial apoptosis caused by METH in endothelial cells |
| GO:0062100 positive regulation of programmed necrotic cell death | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 has been linked to necroptosis/programmed necrosis in some contexts. A specific, less-canonical cell-death output; non-core. Reason: Less-canonical, context-specific cell-death output; non-core. Supporting Evidence: UniProtKB:P10361 In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. |
| GO:0005667 transcription regulator complex | ISO GO_REF:0000121 | ACCEPT | Summary: p53 functions within transcription regulator complexes at target genes. Consistent with the core TF function. Reason: Consistent with core TF function. Supporting Evidence: UniProtKB:P10361 Forms a complex with EP300 and NUPR1; this complex binds CDKN1A promoter leading to transcriptional induction of CDKN1A (By similarity). |
| GO:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the MDM2/E3-ligase-binding annotation central to p53 turnover. Reason: Regulatory interaction (MDM2 etc.); non-core; duplicate. Supporting Evidence: UniProtKB:P10361 Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate (ISS) of the core sequence-specific cis-regulatory DNA-binding annotation. Reason: Core DNA-binding specificity; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:1905856 negative regulation of pentose-phosphate shunt | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 represses TIGAR/G6PD-related metabolism, influencing the pentose-phosphate pathway. A specific metabolic output of p53; non-core. Reason: Specific metabolic output; non-core. Supporting Evidence: UniProtKB:P10361 ALDOB stabilizes the complex inhibiting G6PD activity and keeping oxidative pentose phosphate metabolism in check. |
| GO:0006974 DNA damage response | ISS GO_REF:0000024 | ACCEPT | Summary: The DNA damage response is the central pathway in which p53 acts, linking genotoxic stress to transcriptional reprogramming. This is a core process for p53. Reason: Core pathway role of p53. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Core pathway role: **DNA damage response** linking genotoxic or oncogenic stress to transcriptional reprogramming |
| GO:0006974 DNA damage response | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core DNA damage response annotation. Reason: Core pathway role; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:1990841 promoter-specific chromatin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate (ISS) promoter-specific chromatin binding. Supports the core DNA-binding function. Reason: Supports core DNA/chromatin-binding; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0001094 TFIID-class transcription factor complex binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 contacts the TFIID complex during transactivation. A mechanistic interaction supporting the core TF function. Reason: Mechanistic interaction; ancillary to core MF. Supporting Evidence: UniProtKB:P10361 Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex. |
| GO:0009299 mRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic 'mRNA transcription'; subsumed by the specific Pol II regulation terms. Uninformative as a standalone. Reason: Generic; specific Pol II regulation terms preferred. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0043065 positive regulation of apoptotic process | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the canonical pro-apoptotic regulation annotation. Reason: Canonical core p53 output; duplicate. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core DNA-binding transcription factor activity annotation. Reason: Core molecular function; duplicate of IBA call. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Tp53 encodes p53, a sequence-specific DNA-binding transcription factor** that acts as a central stress-response node and tumor suppressor |
| GO:0003730 mRNA 3'-UTR binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: A reported non-canonical RNA-binding activity (e.g. p53 binding CDK4 mRNA). An in-vitro/non-canonical activity not central to p53 function; weak support. Reason: Non-canonical RNA-binding activity; not an established core function. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P04637 Β· human TP53 SOURCE WEAK OR INFERRED The human donor evidence is a single IDA (PMID:16213212) for non-canonical mRNA binding; weak grounding for a gene-level molecular function in rat. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0034644 cellular response to UV | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: UV is a DNA-damaging stimulus activating p53. Specific instance of the DNA-damage response; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core p53-mediated DNA-damage intrinsic apoptosis annotation. Reason: Core, p53-specific apoptosis process; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0071479 cellular response to ionizing radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ionizing radiation activates the p53 DNA-damage response. Specific stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0071480 cellular response to gamma radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Gamma radiation activates the p53 DNA-damage response. Specific stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0072331 signal transduction by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: This is the defining signaling process for p53 (intracellular signaling induced by p53). A core, p53-specific pathway term. Reason: Core, p53-specific signaling process. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: The p53-mediated intrinsic apoptotic signaling pathway. A core, p53-specific apoptosis process. Reason: Core, p53-specific apoptosis process. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0072717 cellular response to actinomycin D | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Actinomycin D (a nucleolar/transcription stressor) activates p53. Highly specific stimulus; non-core. Reason: Narrow specific stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0002039 p53 binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 self-association (and binding to p53-family members). Reflects homotetramerization; captured more precisely by protein tetramerization. Reason: Self/family-binding; subsumed by tetramerization. Supporting Evidence: UniProtKB:P10361 Forms homodimers and homotetramers (By similarity). |
| GO:0032991 protein-containing complex | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Extremely generic cellular component (any protein complex). Uninformative. Reason: Root-level generic CC; uninformative. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor's complex memberships are documented (IDA/IMP, e.g. PMID:9529249) but by specific complexes; the root-level component term conveys nothing. Supporting Evidence: UniProtKB:P10361 Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. |
| GO:0097718 disordered domain specific binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Reflects p53's intrinsically disordered regions mediating interactions. A generic binding term; non-core. Reason: Generic binding modality; non-core. Supporting Evidence: UniProtKB:P10361 Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) cytoplasm localization (secondary p53 pool). Reason: Secondary localization; non-core; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0006914 autophagy | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 modulates autophagy (context-dependent, both pro- and anti-autophagic). A specific downstream output; non-core. Reason: Specific, context-dependent downstream output; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 also regulates **metabolism, redox, autophagy, ferroptosis, and tumor microenvironment interactions** |
| GO:0042826 histone deacetylase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 interacts with HDACs (e.g. in repressive complexes/Sin3). A specific cofactor interaction; non-core. Reason: Specific cofactor interaction; non-core. Supporting Evidence: PMID:17600529 Oxidative stress regulates IGF1R expression in vascular smooth-muscle cells via p53 and HDAC recruitment. |
| GO:0045892 negative regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53-mediated transcriptional repression. Part of the core dual activator/repressor function; the Pol II-specific child (GO:0000122) is more informative. Reason: Generic repression term; Pol II-specific child preferred. Supporting Evidence: UniProtKB:P10361 The nuclear export signal acts as a transcriptional repression domain. |
| GO:0060333 type II interferon-mediated signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 cross-talks with interferon signaling in some contexts. Peripheral; non-core. Reason: Peripheral signaling cross-talk; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:1905587 positive regulation of outer hair cell apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A highly tissue-specific apoptotic output (cochlear outer hair cells). Far downstream/pleiotropic; non-core. Reason: Highly tissue-specific apoptotic output; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0005515 protein binding | IPI PMID:15872011 Polyamine depletion induces nucleophosmin modulating stabili... | REMOVE | Summary: Generic protein binding for the nucleophosmin (NPM)-p53 complex formed in polyamine-depleted intestinal epithelial (IEC-6) cells. Reason: Bare protein binding is uninformative and the abstract does not establish a more specific p53 molecular function for this interaction, so the generic term is removed; this does not mean the NPM-p53 interaction is false. GOA no longer carries this row. Supporting Evidence: PMID:15872011 Increased NPM interacted with p53 and formed a NPM/p53 complex in polyamine-deficient cells. |
| GO:0045471 response to ethanol | IEP PMID:20961644 Activation of p53 enhances apoptosis and insulin resistance ... | KEEP AS NON CORE | Summary: Specific stimulus (alcohol/ethanol in an alcoholic liver disease model). Peripheral contextual stress response; non-core. Reason: Narrow contextual stimulus; non-core. Supporting Evidence: PMID:20961644 Chronic ethanol consumption in the Long-Evans (LE) rat has been associated with hepatic p53 activation |
| GO:0034614 cellular response to reactive oxygen species | IMP PMID:24817286 Role of reactive oxygen species in p53 activation during cis... | KEEP AS NON CORE | Summary: Experimental support that ROS activate p53 (cisplatin-induced apoptosis in rat mesangial cells). A specific oxidative-stress instance; non-core. Reason: Specific oxidative-stress stimulus; non-core. Supporting Evidence: PMID:24817286 Cisplatin induced apoptotic cell death via caspase-3 activation and PARP cleavage, and also increased p53 activation and ROS production. |
| GO:0032306 regulation of prostaglandin secretion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A highly specific secretory/physiological output transferred by orthology. Far downstream; non-core. Reason: Specific downstream physiological output; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0090276 regulation of peptide hormone secretion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific physiological/secretory output transferred by orthology. Far downstream; non-core. Reason: Specific downstream physiological output; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:2000871 negative regulation of progesterone secretion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A very specific endocrine output transferred by orthology. Far downstream; non-core. Reason: Specific endocrine output; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0008285 negative regulation of cell population proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) antiproliferative output; canonical tumor-suppressive effect via cell-cycle arrest. Reason: Canonical output captured at core level via cell-cycle arrest; duplicate. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific stress-triggered branch of intrinsic apoptosis. p53 participates in ER-stress apoptosis in some contexts; specific/non-core. Reason: Specific stress-branch of apoptosis; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:1900119 positive regulation of execution phase of apoptosis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific apoptosis-execution regulatory term. A downstream detail of p53's pro-apoptotic role; non-core. Reason: Specific apoptosis-execution detail; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0007623 circadian rhythm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 cross-talks with the circadian clock in some contexts. Peripheral/pleiotropic; non-core. Reason: Peripheral cross-talk; non-core. Supporting Evidence: UniProtKB:P10361 Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2. |
| GO:0043153 entrainment of circadian clock by photoperiod | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: A very specific circadian-entrainment role transferred by sequence similarity. Far from p53's core function; weakly supported for rat. Reason: Specific circadian role; weak ISS support, not a core p53 function. Supporting Evidence: UniProtKB:P10361 Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2. |
| GO:0043153 entrainment of circadian clock by photoperiod | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the specific circadian-entrainment annotation. Reason: Specific circadian role; not a core p53 function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET The mouse donor support is an IMP from a single circadian study (PMID:24051492); a specialised organismal context rather than a core p53 role. PR:P02340 Β· mouse Trp53 (PRO entity) SUPPORTS SOURCE BUT NOT TARGET PRO entity for the mouse p53 protein listed alongside the MGI donor; it points at the same PMID:24051492 evidence, so it is the same source rather than a second one. Supporting Evidence: UniProtKB:P10361 Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2. |
| GO:0048512 circadian behavior | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: A behavioral/organismal circadian phenotype transferred by similarity. Far downstream/pleiotropic; non-core. Reason: Organismal behavioral phenotype; not a core p53 function. Supporting Evidence: UniProtKB:P10361 Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2. |
| GO:0048512 circadian behavior | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the circadian-behavior annotation. Reason: Organismal behavioral phenotype; not a core p53 function. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET The mouse donor support is an IMP from the same circadian study (PMID:24051492); an organismal behavioural phenotype, not a p53 molecular role. PR:P02340 Β· mouse Trp53 (PRO entity) SUPPORTS SOURCE BUT NOT TARGET PRO entity for the mouse p53 protein listed alongside the MGI donor; same PMID:24051492 evidence, so no independent support. Supporting Evidence: UniProtKB:P10361 Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate (ISS) of the core DNA-binding transcription factor activity annotation. Reason: Core molecular function; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Tp53 encodes p53, a sequence-specific DNA-binding transcription factor** that acts as a central stress-response node and tumor suppressor |
| GO:0097371 MDM2/MDM4 family protein binding | IPI PMID:23941874 Caveolin-1/PTRF upregulation constitutes a mechanism for med... | ACCEPT | Summary: Direct (IPI) MDM2/MDM4-family binding evidence. Central regulatory interaction; duplicate of the IEA call. Reason: Direct, well-established interaction central to p53 regulation. Supporting Evidence: PMID:23941874 Mechanistically, we found that diabetes-induced oxidative stress upregulated caveolin-1 (Cav-1) and PTRF expression, which in turn sequestered Mdm2 away from p53. |
| GO:0005634 nucleus | IDA PMID:17571083 Mutant ubiquitin found in Alzheimer's disease causes neuriti... | ACCEPT | Summary: Direct (IDA) nuclear localization. Core localization for the TF function. Reason: Core localization; direct evidence. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Nuclear:** stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0046677 response to antibiotic | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific xenobiotic/drug stimulus transferred by orthology. Peripheral; non-core. Reason: Specific drug stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0071456 cellular response to hypoxia | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) hypoxia response. Specific stress stimulus; non-core. Reason: Specific stress stimulus; non-core; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0090200 positive regulation of release of cytochrome c from mitochondria | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A mechanistic step of p53-driven intrinsic apoptosis (cytochrome c release). Supports the core pro-apoptotic role; specific/non-core as a standalone term. Reason: Mechanistic step of intrinsic apoptosis; non-core. Supporting Evidence: PMID:27031958 Elevated p53 expression raised up PUMA expression, which initiated mitochondrial apoptosis by downregulating antiapoptotic Bcl-2, followed by upregulation of proapoptotic Bax |
| GO:2001244 positive regulation of intrinsic apoptotic signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) of the core p53 positive-regulation-of-intrinsic-apoptosis annotation. Reason: Core p53 apoptosis output; duplicate. Supporting Evidence: PMID:27031958 Elevated p53 expression raised up PUMA expression, which initiated mitochondrial apoptosis by downregulating antiapoptotic Bcl-2, followed by upregulation of proapoptotic Bax |
| GO:0034605 cellular response to heat | IEP PMID:11295070 Hyperthermia-induced apoptosis in two rat yolk sac tumor cel... | KEEP AS NON CORE | Summary: Hyperthermia-induced apoptosis (rat yolk sac tumor lines) linking p53 to heat stress. Specific stimulus; non-core. Reason: Specific stress stimulus; non-core. Supporting Evidence: PMID:11295070 Western blot analysis showed an increase in expression of p53, p21WAF1/CIP1, Hsp70 proteins in both cell lines after heat-shock at 43 degrees C for 30 min. |
| GO:0010224 response to UV-B | IEP PMID:22559303 Kinetics of GADD45Ξ±, TP53 and CASP3 gene expression in the r... | KEEP AS NON CORE | Summary: UV-B-induced p53/GADD45/CASP3 response in rat lens. Specific DNA-damage stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: PMID:22559303 The purpose of the present study was to investigate the evolution of expression of mRNA message for the genes for the genome stress sensor GADD45Ξ±, the apoptosis initiator TP53 and the apoptosis executor CASP3 in the rat lens in vivo in response to exposure to UVR around 300 nm. |
| GO:0001221 transcription coregulator binding | IPI PMID:21792911 Analysis of p53 and NF-ΞΊB signaling in modulating the cardio... | KEEP AS NON CORE | Summary: Direct (IPI) interaction with a transcription coregulator (NF-kB context). Supports the core transactivation function via cofactor recruitment. Reason: Cofactor interaction supporting transactivation; ancillary to core MF. Supporting Evidence: PMID:21792911 p53 and NF-ΞΊBp65 binding to co-activator p300 was also increased in AngII treated myocytes. |
| GO:0097252 oligodendrocyte apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A highly cell-type-specific apoptotic output. Far downstream/pleiotropic; non-core. Reason: Cell-type-specific apoptotic output; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0097252 oligodendrocyte apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the oligodendrocyte apoptosis annotation. Reason: Cell-type-specific apoptotic output; non-core; duplicate. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53-mediated transcriptional activation. Part of the core activator function; the Pol II-specific term GO:0045944 is more informative. Reason: Generic activation term; Pol II-specific child preferred. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0016605 PML body | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) PML body localization. Specialized sub-nuclear localization; non-core. Reason: Specialized sub-nuclear localization; non-core; duplicate. Supporting Evidence: UniProtKB:P10361 Recruited into PML bodies together with CHEK2. |
| GO:0016032 viral process | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Generic 'viral process' transferred by orthology (p53 is targeted by viral oncoproteins). Uninformative/peripheral; non-core. Reason: Generic viral-process term; uninformative for p53's own function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH ROLE CONFLATION Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor evidence is an IMP (PMID:22574148) in a viral-infection setting; the generic viral-process term conflates being a viral target with a p53 function. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0030971 receptor tyrosine kinase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific protein interaction transferred by orthology. Peripheral; non-core. Reason: Specific protein interaction; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md phosphorylation, acetylation, methylation and other PTMs affect p53 stability, localization, cofactor recruitment, and target selectivity |
| GO:0048147 negative regulation of fibroblast proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A cell-type-specific antiproliferative output. A specific instance of p53's antiproliferative role; non-core. Reason: Cell-type-specific antiproliferative output; non-core. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0042149 cellular response to glucose starvation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 responds to metabolic/nutrient stress (e.g. via AMPK). Specific stress stimulus; non-core. Reason: Specific metabolic stress stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 also regulates **metabolism, redox, autophagy, ferroptosis, and tumor microenvironment interactions** |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the specific TF-TF binding annotation. Reason: Specific TF-TF interaction; ancillary; duplicate. Supporting Evidence: PMID:10329733 Moreover, Brn-3a and p53 have been shown to bind to adjacent sites in the p2 promoter and to directly interact with one another, both in vitro and in vivo, with this interaction being mediated by the POU domain of Brn-3a and the DNA binding domain of p53. |
| GO:0019899 enzyme binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Generic 'enzyme binding'. Uninformative relative to specific interaction terms (e.g. MDM2, HDAC, kinases). Reason: Generic binding term; uninformative. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor row rests on a single IPI (PMID:17805299); specific interaction terms are far more informative than this generic parent. Supporting Evidence: UniProtKB:P10361 Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. |
| GO:0071466 cellular response to xenobiotic stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic xenobiotic-stress response transferred by orthology. Specific stimulus class; non-core. Reason: Specific stimulus class; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:2000379 positive regulation of reactive oxygen species metabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 modulates ROS/redox metabolism (context-dependent, both pro- and anti-oxidant). A specific metabolic output; non-core. Reason: Specific metabolic output; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 also regulates **metabolism, redox, autophagy, ferroptosis, and tumor microenvironment interactions** |
| GO:0000976 transcription cis-regulatory region binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic parent (ISO) of the specific sequence-specific cis-regulatory binding. Subsumed by GO:0000978. Reason: Generic parent of the more specific DNA-binding term. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0008104 intracellular protein localization | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Very generic process term transferred by orthology. Uninformative. Reason: Generic/uninformative process; not a core p53 function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET The human donor evidence is an IDA (PMID:16507995) for a specific localisation event, and the GOA rows also cite isoform P04637-4; the generic parent term conveys no function. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0008340 determination of adult lifespan | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: An organismal aging/longevity phenotype transferred by orthology. Far downstream/pleiotropic; non-core. Reason: Organismal aging phenotype; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0070245 positive regulation of thymocyte apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A cell-type-specific apoptotic output (thymocytes). A classic p53-dependent apoptosis instance, but cell-type-specific; non-core. Reason: Cell-type-specific apoptotic output; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0097371 MDM2/MDM4 family protein binding | ISO GO_REF:0000121 | ACCEPT | Summary: Duplicate (ISO) MDM2/MDM4 binding. Central regulatory interaction. Reason: Direct interaction central to p53 regulation; duplicate. Supporting Evidence: UniProtKB:P10361 Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. |
| GO:0090399 replicative senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific senescence subtype. p53 enforces replicative senescence; a downstream instance of the senescence program; non-core. Reason: Specific senescence subtype; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0090403 oxidative stress-induced premature senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific senescence subtype induced by oxidative stress. Downstream instance of the senescence program; non-core. Reason: Specific senescence subtype; non-core. Supporting Evidence: PMID:23941874 This process resulted in the activation of a p53/p21-dependent pathway and the induction of premature senescence in DFs. |
| GO:0006983 ER overload response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific ER-stress response transferred by orthology. Specific stimulus; non-core. Reason: Specific stress response; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0042981 regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the generic apoptosis-regulation annotation; subsumed by p53-specific terms. Reason: Generic; p53-specific apoptosis terms preferred; duplicate. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: The DNA-damage-response signaling specifically mediated by p53. A core, p53-specific pathway term integrating DNA damage with p53 signaling. Reason: Core, p53-specific DNA-damage signaling process. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Core pathway role: **DNA damage response** linking genotoxic or oncogenic stress to transcriptional reprogramming |
| GO:0002020 protease binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific protein interaction transferred by orthology. Peripheral; non-core. Reason: Specific protein interaction; non-core. Supporting Evidence: UniProtKB:P10361 Interacts with USP7 and SYVN1. |
| GO:0051721 protein phosphatase 2A binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A specific interaction (PP2A regulating p53 phosphorylation). A regulatory interaction; non-core. Reason: Specific regulatory interaction; non-core. Supporting Evidence: UniProtKB:P10361 regulates stress-induced TP53-dependent inhibition of cell proliferation. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:16330492 Ubiquitin-dependent degradation of p53 protein despite phosp... | KEEP AS NON CORE | Summary: Direct (IPI) E3 ligase binding (acetaminophen-induced p53 degradation context). Captures the MDM2/E3-ligase interaction underlying p53 turnover; non-core. Reason: Regulatory E3-ligase interaction; non-core. Supporting Evidence: PMID:16330492 Immunoblot analysis of the immunoprecipitated p53 revealed that increased amounts of murine double minute 2 (mdm2) and ubiquitin were bound to p53 during its degradation. |
| GO:0016604 nuclear body | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic parent of PML body. p53 localizes to nuclear bodies; specialized sub-nuclear localization; non-core. Reason: Specialized sub-nuclear localization; non-core. Supporting Evidence: UniProtKB:P10361 Recruited into PML bodies together with CHEK2. |
| GO:0007265 Ras protein signal transduction | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A signaling cross-talk transferred by orthology (oncogene-induced p53 activation). Peripheral; non-core. Reason: Peripheral signaling cross-talk; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0005515 protein binding | IPI PMID:8389468 Physical and functional interaction between WT1 and p53 prot... | MODIFY | Summary: IPI for p53 binding WT1, a sequence-specific zinc-finger transcription factor; the interaction modulates the transactivation activity of both proteins. Reason: Generic protein binding is uninformative. WT1 is a DNA-binding RNA polymerase II transcription factor, so the interaction is better captured by RNA polymerase II-specific DNA-binding transcription factor binding (already used for the rat Brn-3a interaction). Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:8389468 WT1 encodes a transcription factor which binds to the EGR1 consensus sequence, mediating transcriptional repression. PMID:8389468 We now demonstrate that p53, the product of a tumor-suppressor gene with ubiquitous expression, physically associates with WT1 in transfected cells. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:8389468 Physical and functional interaction between WT1 and p53 prot... | KEEP AS NON CORE | Summary: Direct (IDA) evidence that p53 represses transcription (WT1/p53 functional interaction). Supports the core dual activator/repressor function; generic term, Pol II-specific child preferred. Reason: Generic repression term; supports core repressor activity, Pol II-specific child preferred. Supporting Evidence: PMID:8389468 The interaction between WT1 and p53 modulates their ability to transactivate their respective targets. |
| GO:0010332 response to gamma radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Gamma radiation activates the p53 DNA-damage response. Specific stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0031571 mitotic G1 DNA damage checkpoint signaling | ISO GO_REF:0000121 | ACCEPT | Summary: p53 enforces the G1 DNA-damage checkpoint (via p21). A specific, mechanistically central output of the p53 DNA-damage response. Reason: A defining, specific p53-mediated checkpoint output of the DNA-damage response. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:11278372 Stabilization and activation of p53 by the coactivator prote... | ACCEPT | Summary: Direct (IDA) evidence of p53-driven Pol II transactivation (TAFII31 coactivator). Core transcriptional activator function. Reason: Core function; direct evidence of Pol II transactivation. Supporting Evidence: PMID:11278372 TAF(II)31-mediated p53 stabilization results in activation of p53-mediated transcriptional activity and leads to p53-dependent growth arrest in fibroblasts. |
| GO:0051087 protein-folding chaperone binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 interacts with chaperones (e.g. HSP90/HSP70) that regulate its folding/stability. A regulatory interaction; non-core. Reason: Specific regulatory chaperone interaction; non-core. Supporting Evidence: UniProtKB:P10361 Interacts with HSP90AB1 (PubMed:8663025). |
| GO:0006979 response to oxidative stress | IEP PMID:17600529 Oxidative stress regulates IGF1R expression in vascular smoo... | KEEP AS NON CORE | Summary: Expression-pattern evidence for p53 in oxidative-stress response (IGF1R/HDAC in VSMCs). Specific stress stimulus; non-core. Reason: Specific stress stimulus; non-core. Supporting Evidence: PMID:17600529 Oxidative stress also induced p53 phosphorylation and apoptosis in VSMCs. |
| GO:0010038 response to metal ion | IEP PMID:17466256 Apoptosis and inhibition of gap-junctional intercellular com... | MARK AS OVER ANNOTATED | Summary: IEP from a study comparing the platinum(IV) complex LA-12 with cisplatin: p53 is activated as a consequence of drug-induced DNA damage. Reason: Changed from KEEP_AS_NON_CORE. The platinum drug acts by attacking DNA and p53 activation is the DNA damage response the gene already carries; 'response to metal ion' overstates this as a metal-specific response. Supporting Evidence: PMID:17466256 LA-12 induced apoptosis much more efficiently than did CDDP due to a combination of rapid penetration into the cell and attack on DNA, leading to fast activation of p53 and caspase-3. |
| GO:0031000 response to caffeine | IEP PMID:16544096 Activation of p53 signaling initiates apoptotic death in a c... | MARK AS OVER ANNOTATED | Summary: IEP from a Parkinson's disease cell model in which caffeine was used as an ATM kinase inhibitor to block 6-hydroxydopamine-induced p53 Ser-15 phosphorylation. Reason: Changed from KEEP_AS_NON_CORE. Caffeine served as a pharmacological ATM inhibitor, not as a stimulus to which p53 physiologically responds; the term overstates the experiment. Supporting Evidence: PMID:16544096 We found that 6-hydroxydopamine induced phosphorylation of ataxia telangiectasia mutated (ATM) kinase an event integral to p53 activation and caffeine (ATM kinase inhibitor) inhibited Ser-15 phosphorylation. |
| GO:0033552 response to vitamin B3 | IEP PMID:17516866 Niacin deficiency alters p53 expression and impairs etoposid... | KEEP AS NON CORE | Summary: Niacin (vitamin B3) deficiency alters p53 expression in rat bone marrow. A specific nutritional stimulus; non-core. Reason: Specific nutritional stimulus; non-core. Supporting Evidence: PMID:17516866 ND diet alone caused overexpression of two distinct isoforms of p53. |
| GO:0043200 response to amino acid | IEP PMID:17542038 Glutamine supplementation prevents exercise-induced neutroph... | KEEP AS NON CORE | Summary: A specific nutritional stimulus (glutamine). Peripheral; non-core. Reason: Specific nutritional stimulus; non-core. Supporting Evidence: PMID:17542038 A single session of exercise increased p38 MAPK and JNK phosphorylation and p53 and caspase 3 expression. |
| GO:0002687 positive regulation of leukocyte migration | IMP PMID:18317410 Inhibition of p53 by pifithrin-alpha reduces myocyte apoptos... | KEEP AS NON CORE | Summary: A specific physiological output (leukocyte transmigration in aged rat hearts, via pifithrin-alpha p53 inhibition). Far downstream/pleiotropic; non-core. Reason: Specific tissue-level physiological output; non-core. Supporting Evidence: PMID:18317410 Inhibition of p53 by pifithrin-alpha reduces myocyte apoptosis and leukocyte transmigration in aged rat hearts following 24 hours of reperfusion. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:18336558 Effects of chronic treatment with valproate and oxcarbazepin... | KEEP AS NON CORE | Summary: A specific xenobiotic stimulus (valproate/oxcarbazepine). Peripheral; non-core. Reason: Specific xenobiotic stimulus; non-core. Supporting Evidence: PMID:18336558 Intensity of P53 labeling increased, while intensity of TGF beta 1, IGF-1, and GDF-9 immunoreactivity decreased significantly in all drug groups compared with control group |
| GO:0009411 response to UV | IEP PMID:17724205 p53 expression and apoptosis in the lens after ultraviolet r... | KEEP AS NON CORE | Summary: UV-induced p53 expression/apoptosis in the rat lens. Specific DNA-damage stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: PMID:17724205 To localize p53 protein and active caspase-3 in the albino rat lens and to compare p53 mRNA and active caspase-3 expression in ultraviolet radiation (UVR) 300 nm exposed lenses and their contralateral nonexposed controls. |
| GO:0010165 response to X-ray | IEP PMID:17699727 A novel animal model to investigate fractionated radiotherap... | KEEP AS NON CORE | Summary: Radiotherapy-induced p53/apoptosis in a rat mucositis model. Specific DNA-damage stimulus; non-core. Reason: Specific DNA-damage stimulus; non-core. Supporting Evidence: PMID:17699727 Expression of p53, nuclear factor-kappaB, COX-1, and COX-2 was increased in the irradiated intestinal sections. |
| GO:0032526 response to retinoic acid | IEP PMID:17962954 Retinoic acid downregulates microRNAs to induce abnormal dev... | KEEP AS NON CORE | Summary: A specific stimulus (retinoic acid in a spina bifida model). Peripheral; non-core. Reason: Specific stimulus; non-core. Supporting Evidence: PMID:17962954 There is a dramatic decrease in the expression of miR-9/9*, miR-124a and miR-125b, and Bcl2 and P53 as well in the sacral cord from E13. |
| GO:0034097 response to cytokine | IEP PMID:17651018 IFN-gamma promotes apoptosis of the uterus and placenta in p... | KEEP AS NON CORE | Summary: IFN-gamma-associated apoptosis in pregnant rat uterus/placenta. Specific cytokine stimulus; non-core. Reason: Specific cytokine stimulus; non-core. Supporting Evidence: PMID:17651018 IFN regulatory factor-1 (IRF-1), FasL, and p53 expressions were modulated by IFN-gamma during the entire pregnancy. |
| GO:0045787 positive regulation of cell cycle | IMP PMID:18026139 Activation of the p53-p21(Cip1) pathway is required for CDK2... | KEEP AS NON CORE | Summary: A context-specific positive cell-cycle effect (p53-p21 required for CDK2/S-phase entry in primary rat hepatocytes). p53 canonically arrests the cell cycle; this opposite-direction effect is context-specific and non-core. Reason: Context-specific positive effect; p53's core cell-cycle role is arrest. Supporting Evidence: PMID:18026139 Activation of the p53-p21(Cip1) pathway is required for CDK2 activation and S-phase entry in primary rat hepatocytes. |
| GO:0048662 negative regulation of smooth muscle cell proliferation | IMP PMID:17659301 Induction of p53 by GKLF is essential for inhibition of prol... | KEEP AS NON CORE | Summary: A cell-type-specific antiproliferative output (VSMCs, via GKLF-induced p53). A specific instance of p53's antiproliferative role; non-core. Reason: Cell-type-specific antiproliferative output; non-core. Supporting Evidence: PMID:17659301 Induction of p53 by GKLF is essential for inhibition of proliferation of vascular smooth muscle cells. |
| GO:0055093 response to hyperoxia | IEP PMID:18337831 Hyperbaric oxygen attenuates apoptosis and decreases inflamm... | KEEP AS NON CORE | Summary: A specific oxidative stimulus (hyperbaric oxygen/ischemic wound). Peripheral; non-core. Reason: Specific oxidative stimulus; non-core. Supporting Evidence: PMID:18337831 Analysis of ischemic wound tissue extracts demonstrated significantly reduced expression of HIF-1alpha, p53, and BNip3. |
| GO:1901423 response to benzene | IEP PMID:18093815 Differentially expressed pro- and anti-apoptogenic genes in ... | KEEP AS NON CORE | Summary: A specific xenobiotic stimulus (benzene exposure, lung epithelia). Peripheral; non-core. Reason: Specific xenobiotic stimulus; non-core. Supporting Evidence: PMID:18093815 Rats exposed to benzene via inhalation (300 ppm) for 7 days showed a significant upregulation of proapoptotic gene expression for p53, Bax, and Bad |
| GO:0000785 chromatin | IDA PMID:15632413 Combinatorial control of the bradykinin B2 receptor promoter... | ACCEPT | Summary: Direct (IDA) chromatin localization (bradykinin B2 receptor promoter). Supports the core DNA-binding function. Reason: Core localization for DNA-binding; direct evidence. Supporting Evidence: PMID:15632413 The rat B2R 5'-flanking region has a highly conserved cis-acting enhancer in the proximal promoter consisting of contiguous binding sites for the transcription factors cAMP response element binding protein (CREB), p53, and Kruppel-like factor (KLF-4). |
| GO:0005667 transcription regulator complex | IDA PMID:15632413 Combinatorial control of the bradykinin B2 receptor promoter... | ACCEPT | Summary: Direct (IDA) evidence that p53 acts within a transcription regulator complex (with CREB, KLF-4, CBP on the B2R promoter). Consistent with the core TF function. Reason: Consistent with core TF function; direct evidence. Supporting Evidence: PMID:15632413 Several lines of evidence indicate that cooperative interactions among the three transcription factors occur in vivo during terminal nephron differentiation |
| GO:0043565 sequence-specific DNA binding | IDA PMID:15632413 Combinatorial control of the bradykinin B2 receptor promoter... | ACCEPT | Summary: Direct (IDA) evidence of p53 sequence-specific DNA binding at a target promoter. This is the core DNA-binding molecular function. Reason: Core molecular function; direct experimental evidence of sequence-specific DNA binding. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:0003682 chromatin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic chromatin binding; subsumed by the specific sequence-specific and promoter-specific binding terms. Reason: Generic; specific DNA/chromatin binding terms preferred. Supporting Evidence: UniProtKB:P10361 Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:16688778 Multiple apoptotic pathways induced by p53-dependent acidifi... | ACCEPT | Summary: Direct functional (IMP) evidence of p53-dependent apoptosis (benzo[a]pyrene-exposed hepatic cells). Core pro-apoptotic role. Reason: Core pro-apoptotic role; experimentally supported. Supporting Evidence: PMID:16688778 Multiple apoptotic pathways induced by p53-dependent acidification |
| GO:0051453 regulation of intracellular pH | IMP PMID:16688778 Multiple apoptotic pathways induced by p53-dependent acidifi... | KEEP AS NON CORE | Summary: A specific output (p53-dependent acidification in the same benzo[a]pyrene study). An unusual/specific downstream effect; non-core. Reason: Specific, unusual downstream effect; non-core. Supporting Evidence: PMID:16688778 Multiple apoptotic pathways induced by p53-dependent acidification |
| GO:0046982 protein heterodimerization activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: p53 can heterodimerize/hetero-oligomerize with family members (p63/p73) or interact with partners. A binding modality; subsumed by tetramerization for the core homo-oligomer. Reason: Binding modality; non-core relative to homotetramerization. Supporting Evidence: UniProtKB:P10361 Found in a complex with CABLES1 and TP73. |
| GO:0016363 nuclear matrix | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: A sub-nuclear localization transferred by orthology. Specialized; non-core. Reason: Specialized sub-nuclear localization; non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0065003 protein-containing complex assembly | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Generic complex-assembly term (reflects tetramer/complex formation). Uninformative relative to protein tetramerization. Reason: Generic; tetramerization is the informative term. Supporting Evidence: UniProtKB:P10361 Forms homodimers and homotetramers (By similarity). |
| GO:0005515 protein binding | IPI PMID:12464630 A nucleolar mechanism controlling cell proliferation in stem... | REMOVE | Summary: Generic protein binding for the interaction of p53 with the nucleolar GTP-binding protein nucleostemin (GNL3). Reason: Bare protein binding is uninformative and the abstract (full text not cached) does not define a more specific p53 molecular function for the interaction, so the generic term is removed; this does not mean the nucleostemin-p53 interaction is false. Supporting Evidence: PMID:12464630 The N-terminal basic domain specifies nucleolar localization, the p53 interaction, and is required for the cell death caused by overexpression. |
| GO:1904584 cellular response to polyamine macromolecule | IEP PMID:11502571 Polyamine depletion stabilizes p53 resulting in inhibition o... | KEEP AS NON CORE | Summary: A specific stimulus (polyamine depletion stabilizing p53 in intestinal epithelium). Peripheral; non-core. Reason: Specific stimulus; non-core. Supporting Evidence: PMID:11502571 Polyamine depletion stabilizes p53 resulting in inhibition of normal intestinal epithelial cell proliferation. |
| GO:2000279 negative regulation of DNA biosynthetic process | IMP PMID:11502571 Polyamine depletion stabilizes p53 resulting in inhibition o... | KEEP AS NON CORE | Summary: p53-dependent inhibition of DNA synthesis/proliferation (polyamine-depletion context). A specific instance of p53's antiproliferative/checkpoint role; non-core. Reason: Specific antiproliferative output; non-core. Supporting Evidence: PMID:11502571 Polyamine depletion stabilizes p53 resulting in inhibition of normal intestinal epithelial cell proliferation. |
| GO:0003677 DNA binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate (ISS) generic DNA binding; subsumed by the specific sequence-specific DNA-binding terms. Reason: Generic; specific DNA-binding terms preferred; duplicate. Supporting Evidence: UniProtKB:P10361 Binds DNA as a homotetramer. |
| GO:0005507 copper ion binding | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: p53 can bind metal ions (zinc is structurally required in the DBD; copper binding has been reported in vitro). Copper binding is not an established physiological function and ISS support is weak. Reason: Copper binding is not an established p53 function (the structurally required metal is zinc); weak ISS support. Supporting Evidence: UniProtKB:P10361 Binds 1 zinc ion per subunit. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Duplicate (ISS) nucleus localization. Core localization. Reason: Core localization; duplicate. Supporting Evidence: UniProtKB:P10361 Cytoplasm {ECO:0000250|UniProtKB:P04637}. Nucleus {ECO:0000250|UniProtKB:P04637}. |
| GO:0005730 nucleolus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: p53 localizes to the nucleolus in some contexts (nucleolar stress sensing). A specialized sub-nuclear localization; non-core. Reason: Specialized sub-nuclear localization; non-core. Supporting Evidence: UniProtKB:P10361 Interacts (via oligomerization region) with NOP53; the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of TP53. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate (ISS) cytoplasm localization (secondary pool). Reason: Secondary localization; non-core; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Duplicate (ISS) mitochondrion localization (transcription-independent apoptosis). Secondary; non-core. Reason: Secondary localization; non-core; duplicate. Supporting Evidence: UniProtKB:P10361 Translocates to mitochondria upon oxidative stress. |
| GO:0006289 nucleotide-excision repair | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: p53 facilitates nucleotide-excision repair (e.g. via transactivation of repair genes such as DDB2/XPC). A genuine DNA-repair-supporting role downstream of its TF function; non-core. Reason: DNA-repair-supporting role downstream of the core DNA-damage response; non-core. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0030308 negative regulation of cell growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A generic antigrowth term; subsumed by the specific cell-cycle-arrest/antiproliferation terms. Canonical tumor-suppressive output. Reason: Generic; specific arrest/antiproliferation terms preferred. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0006289 nucleotide-excision repair | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) of the NER-supporting role. Reason: DNA-repair-supporting role; non-core; duplicate. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0005507 copper ion binding | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Duplicate (ISO) of the speculative copper-binding annotation. Reason: Not an established p53 function (zinc is the structural metal); weak support. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P04637 Β· human TP53 SOURCE WEAK OR INFERRED The human donor evidence is a single in vitro metal-binding IDA (PMID:7824276); zinc, not copper, is p53's established structural metal. Supporting Evidence: UniProtKB:P10361 Binds 1 zinc ion per subunit. |
| GO:0030308 negative regulation of cell growth | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) generic antigrowth term. Reason: Generic; specific arrest terms preferred; duplicate. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0003677 DNA binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) generic DNA binding; subsumed by specific terms. Reason: Generic; specific DNA-binding terms preferred; duplicate. Supporting Evidence: UniProtKB:P10361 Binds DNA as a homotetramer. |
| GO:0005730 nucleolus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) nucleolus localization (nucleolar stress sensing). Specialized; non-core. Reason: Specialized sub-nuclear localization; non-core; duplicate. Supporting Evidence: UniProtKB:P10361 Interacts (via oligomerization region) with NOP53; the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of TP53. |
| GO:0006355 regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Duplicate (ISO) generic transcription-regulation term; subsumed by the specific Pol II terms. Reason: Generic parent; non-core; duplicate. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed ISO row for transcriptional repression; p53 represses a subset of Pol II targets (e.g. Bcl-2). Reason: Mouse Trp53 (MGI:98834) donor with acts_upstream_of_or_within qualifier (mouse IDA/IGI). Consistent with the sibling ACCEPT: sequence-specific repression is part of the core p53 transcription-factor function. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. UniProtKB:P10361 The nuclear export signal acts as a transcriptional repression domain. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed GO:0000122 ISO row; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor; p53 represses Pol II targets as part of its core dual activator/repressor function, consistent with the sibling ACCEPT. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed GO:0000122 ISO row; human TP53 canonical plus isoform P04637-4 donors. Reason: Human TP53 donor (P04637 with isoform P04637-4 cited); the isoform citation records what was tested and does not make repression isoform-specific. Consistent with sibling ACCEPT. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: IBA row for chromatin with is_active_in qualifier, sibling of the reviewed chromatin IBA row. p53 acts on chromatin at p53 response elements. Reason: PAINT node PTN000893833 places chromatin-associated activity at the p53/p63/p73 family ancestor; rat Tp53 is inside that clade and binds response elements on chromatin. Consistent with sibling ACCEPT. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0000976 transcription cis-regulatory region binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed GO:0000976 ISO row; human TP53 canonical plus isoform P04637-2 donors. Correct but generic parent of the sequence-specific Pol II cis-regulatory binding term. Reason: Human TP53 donor (P04637, P04637-2). Kept as non-core like its siblings because GO:0000978 captures the specific core activity. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: RNA polymerase II transcription regulatory region sequence-specific DNA binding, transferred from mouse Trp53 (mouse IDA PMID:22897442). Direct parent of the accepted GO:0000978 and a correct statement of p53's sequence-specific DNA binding. Reason: Mouse Trp53 (MGI:98834) donor. Sequence-specific Pol II regulatory-region binding is the core p53 molecular activity. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed GO:0000978 rows; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor; core sequence-specific DNA binding, consistent with sibling ACCEPT. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Central DNA-binding domain (DBD)**: mediates sequence-specific recognition of response elements |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed GO:0001228 ISO row; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor; p53 is a sequence-specific Pol II transcriptional activator (e.g. CDKN1A). Consistent with sibling ACCEPT and core_functions. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators UniProtKB:P10361 Forms a complex with EP300 and NUPR1; this complex binds CDKN1A promoter leading to transcriptional induction of CDKN1A (By similarity). |
| GO:0001701 in utero embryonic development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: In utero embryonic development transferred from mouse Trp53 (MGI:98834) acts_upstream_of_or_within (mouse IGI PMID:17325035, PMID:26334721, PMID:9288110). Two donors are compound mutants (Gcn5, Jmjd5) in which p53 activation contributes to embryonic lethality; the third (PMID:9288110, Msh2) runs the other way, reporting female embryonic lethality in mice lacking both Msh2 and p53, so it is a loss-of-function interaction rather than p53 activation. Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting; the developmental defect reflects inappropriate p53 activation (apoptosis/arrest) when negative regulators or ribosome/chromatin factors are lost, not a p53 role in executing embryonic development. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant (or sensitized) genotype in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:17325035 Here we show that deletion of p53 allows Gcn5(-/-) embryos to survive longer, but Gcn5(-/-) p53(-/-) embryos still die in midgestation. PMID:26334721 Genetic studies have shown that aberrant activation of p53 signaling leads to embryonic lethality. |
| GO:0001701 in utero embryonic development | ISO NOT GO_REF:0000121 | UNDECIDED | Summary: NOT acts_upstream_of_or_within in utero embryonic development, transferred from mouse Trp53 (MGI:98834); the mouse source is IGI PMID:9425892, a correspondence reporting no female embryonic lethality in Msh2/p53 double-null mice. Reason: The cached source is a comment letter with no abstract text, and it addresses one compound genotype; the same donor also carries the positive annotation from other compound mutants. A negated developmental statement transferred by orthology cannot be adjudicated from the available text. Propagation Review Root cause: UNRESOLVED Sources checked: MGI:MGI:98834 Β· mouse Trp53 UNRESOLVED Mouse IGI NOT annotation from a correspondence (PMID:9425892) about Msh2/p53 double-null mice; no abstract text available, and the same donor also carries the positive annotation. |
| GO:0001756 somitogenesis | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Somitogenesis transferred from mouse Trp53 (MGI:98834). The mouse row is an IGI whose recorded reference is PMID:17320900, a Dlk1/Notch adipogenesis study in cultured mesenchymal cells; its abstract mentions neither p53 nor somites. MGI records the IGI partner as Kat2a (Gcn5; MGI:1343101). Reason: The recorded donor reference cannot be matched to the claim from the cached text (abstract only, no p53, no somitogenesis), so no mechanism is taken from it. The only Kat2a/p53 compound-mutant evidence on somites that can be read is PMID:17325035, which reports that eliminating p53 allows Gcn5-null embryos to develop somites; whether that paper is the intended source is for MGI to confirm. Under either reading the role is the same, namely p53 acting upstream of a lineage-survival phenotype, which is not participation in somite formation, so the term overstates p53's involvement. The action rests on that participation argument and not on the unverifiable reference; if the recorded reference is confirmed as intended, the row should be revisited. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 UNRESOLVED Mouse IGI with partner Kat2a (MGI:1343101); the recorded reference PMID:17320900 is a Dlk1 adipogenesis cell-culture paper whose abstract does not mention p53 or somites, so the donor evidence cannot be verified from the cached text. The Kat2a/p53 somite result in PMID:17325035 is cited as the nearest readable evidence, not as the confirmed source. Supporting Evidence: PMID:17325035 We show here that elimination of the p53 tumor suppressor allows Gcn5 β/β embryos to survive longer and to develop somites. |
| GO:0001836 release of cytochrome c from mitochondria | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Release of cytochrome c from mitochondria transferred from mouse Trp53 (mouse IDA/IGI). p53 promotes mitochondrial outer membrane permeabilization through BAX/PUMA induction and direct BCL-2-family interactions. Reason: Mouse Trp53 donor. Genuine apoptotic output, consistent with the reviewed positive regulation of cytochrome c release row; downstream of the core TF function. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 can trigger apoptosis through direct interactions with anti-apoptotic BCL-2 family members at mitochondria PMID:27031958 Elevated p53 expression raised up PUMA expression, which initiated mitochondrial apoptosis by downregulating antiapoptotic Bcl-2, followed by upregulation of proapoptotic Bax |
| GO:0002309 T cell proliferation involved in immune response | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: T cell proliferation involved in immune response transferred from mouse Trp53 (mouse IGI PMID:16357222, S6 ribosomal protein deletion in T cells). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting; the developmental defect reflects inappropriate p53 activation (apoptosis/arrest) when negative regulators or ribosome/chromatin factors are lost, not a p53 role in executing T cell proliferation. The study describes a p53-dependent checkpoint that eliminates defective T cells. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant (or sensitized) genotype in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:16357222 Genetic inactivation of p53 tumor suppressor rescued development of S6-homozygous null thymocytes and proliferative defect of S6-heterozygous T cells. |
| GO:0002326 B cell lineage commitment | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: B cell lineage commitment transferred from mouse Trp53 (mouse IMP PMID:8788039, Fas surface expression in lymphoid subsets). Reason: Mouse Trp53 donor. The source measured Fas-expressing lymphocyte subset proportions in p53-null mice; altered subset ratios do not show p53 acting in lineage commitment. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse IMP measuring Fas-expressing lymphocyte subsets in p53-null mice; does not show a role in lineage commitment. Supporting Evidence: PMID:8788039 Although the products of neither bcl-2 nor p53 genes are essential for Fas cell surface expression on hematopoietic cells, these repressor and effector genes, respectively, of programmed cell death affect distinct subsets of lymphoid lineage cells at different stages of lymphopoiesis. |
| GO:0002360 T cell lineage commitment | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: T cell lineage commitment transferred from mouse Trp53 (mouse IMP PMID:8788039). Reason: Mouse Trp53 donor. Same Fas-expression study as the B-cell row; subset distribution changes do not establish a role in lineage commitment. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse IMP measuring Fas-expressing lymphocyte subsets in p53-null mice; does not show a role in lineage commitment. Supporting Evidence: PMID:8788039 Although the products of neither bcl-2 nor p53 genes are essential for Fas cell surface expression on hematopoietic cells, these repressor and effector genes, respectively, of programmed cell death affect distinct subsets of lymphoid lineage cells at different stages of lymphopoiesis. |
| GO:0002931 response to ischemia | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Response to ischemia transferred from mouse Trp53 (mouse IMP PMID:22044588). p53 is activated by ischemic stress and aggravates cardiac damage. Reason: Mouse Trp53 donor. Context-specific stress response downstream of p53 stabilization; non-core. Supporting Evidence: PMID:22044588 Inhibition of tumor suppressor p53 is cardioprotective against ischemic injury and provides resistance to subsequent cardiac remodeling. |
| GO:0003682 chromatin binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed chromatin binding ISO row; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor. True but generic; p53 binds response elements in chromatin and recruits coactivators. Non-core, consistent with sibling. Supporting Evidence: UniProtKB:P10361 Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. |
| GO:0003700 DNA-binding transcription factor activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed GO:0003700 rows; human TP53 donor. Correct but less specific than the Pol II-specific TF term. Reason: Human TP53 donor. Kept as non-core; GO:0000981 captures the core function. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA row for nucleus with is_active_in qualifier, sibling of the reviewed nucleus IBA row. Reason: PAINT node PTN000893833 places nuclear activity at the p53-family ancestor; rat Tp53 is inside that clade and acts as a nuclear transcription factor. Consistent with sibling ACCEPT. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleus (is_active_in) transferred from human TP53. Reason: Human TP53 (UniProtKB:P04637) donor. The nucleus is where p53 performs its core transcription-factor activity. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Nucleus transferred from pig TP53 (RGD:14013963). Reason: Pig TP53 donor curated at RGD. Core localization of a nuclear transcription factor; consistent with the other nucleus rows. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription UniProtKB:P10361 Cytoplasm {ECO:0000250|UniProtKB:P04637}. Nucleus {ECO:0000250|UniProtKB:P04637}. |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed nucleus ISO rows; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor. Core localization. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed nucleus ISO rows; human TP53 donor rows citing isoforms P04637-1, -2, -3, -7 and -8. Reason: Human TP53 donor; the isoform citations record what was tested. Nuclear localization of the canonical protein is core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0005634 nucleus | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed nucleus ISO rows; human TP53 canonical plus isoform P04637-4 donors. Reason: Human TP53 donor (P04637, P04637-4). Core localization. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md stabilized p53 forms tetramers in the nucleus and binds DNA response elements to regulate transcription |
| GO:0005657 replication fork | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Replication fork transferred from mouse Trp53 (mouse IDA PMID:15364958). In replication-stressed cells p53 forms foci that colocalize with 53BP1, BLM and gamma-H2AX at stalled forks. Reason: Mouse Trp53 donor. Supported by the donor paper, but recruitment to stalled forks is a stress-context localization rather than the site of the core TF activity. Supporting Evidence: PMID:15364958 Ξ³-H2AX, 53BP1, BLM, and p53 colocalize and accumulate with similar kinetics. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed cytoplasm ISO rows; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor. p53 shuttles and has a cytoplasmic pool; non-core, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling UniProtKB:P10361 Cytoplasm {ECO:0000250|UniProtKB:P04637}. Nucleus {ECO:0000250|UniProtKB:P04637}. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed cytoplasm ISO rows; human TP53 donor rows citing isoforms P04637-2, -3, -7, -8 and -9. Reason: Human TP53 donor; isoform citations record what was tested. Non-core cytoplasmic pool, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed cytoplasm ISO rows; human TP53 canonical plus isoform P04637-4 donors. Reason: Human TP53 donor (P04637, P04637-4). Non-core, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed mitochondrion ISO rows; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor. Stress-induced mitochondrial translocation underlies transcription-independent apoptosis/necrosis; non-core. Supporting Evidence: UniProtKB:P10361 Translocates to mitochondria upon oxidative stress. PMID:24101517 Here we report that the mammalian homolog of the yeast mitochondrial disulfide relay protein Mia40 (CHCHD4) is necessary for the respiratory-dependent translocation of p53 into the mitochondria. |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrial matrix transferred from mouse Trp53 (mouse IDA PMID:22726440). Under oxidative stress or ischemia p53 accumulates in the matrix and interacts with cyclophilin D (PPIF) to open the permeability transition pore. Reason: Mouse Trp53 donor. The donor paper directly shows matrix accumulation; a stress-induced, transcription-independent localization, so non-core. Supporting Evidence: PMID:22726440 In response to oxidative stress and ischemia, p53 protein accumulates in the mitochondrial matrix and triggers PTP opening, mPT and necrosis by physical interaction with the critical PTP regulator CypD. UniProtKB:P10361 Endoplasmic reticulum {ECO:0000250|UniProtKB:P04637}. Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrial matrix transferred from human TP53 (human EXP rows incl. PMID:22726440). Reason: Human TP53 (UniProtKB:P04637) donor. Matrix accumulation under oxidative stress is experimentally supported; non-core. Supporting Evidence: PMID:22726440 In response to oxidative stress and ischemia, p53 protein accumulates in the mitochondrial matrix and triggers PTP opening, mPT and necrosis by physical interaction with the critical PTP regulator CypD. |
| GO:0005759 mitochondrial matrix | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial matrix by ISS from human TP53. Reason: ISS from human TP53 (UniProtKB:P04637), matching the UniProt subcellular-location statement. Stress-induced and non-core. Supporting Evidence: UniProtKB:P10361 Endoplasmic reticulum {ECO:0000250|UniProtKB:P04637}. Mitochondrion matrix PMID:22726440 In response to oxidative stress and ischemia, p53 protein accumulates in the mitochondrial matrix and triggers PTP opening, mPT and necrosis by physical interaction with the critical PTP regulator CypD. |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Endoplasmic reticulum transferred from human TP53 (human EXP PMID:17170702). The source shows p53 being sequestered and degraded by the ER-resident E3 ligase synoviolin. Reason: Human TP53 donor. ER association reflects p53 as a degradation substrate of synoviolin rather than a compartment where p53 functions; consistent with the reviewed IEA ER row. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET Human EXP (PMID:17170702) shows p53 sequestered and degraded by the ER-resident ligase synoviolin; ER association as a substrate, not a functional compartment. Supporting Evidence: PMID:17170702 Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Endoplasmic reticulum by ISS from human TP53. Reason: ISS from human TP53 (UniProtKB:P04637); same basis and judgment as the ISO ER rows: p53 is a substrate of an ER-resident ligase, not a resident ER protein. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET Human EXP (PMID:17170702) shows p53 sequestered and degraded by the ER-resident ligase synoviolin; ER association as a substrate, not a functional compartment. Supporting Evidence: PMID:17170702 Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed cytosol ISO row; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor. Cytosolic pool is real but non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md It is also present in the **cytoplasm** and can relocalize to **mitochondria** for transcription-independent apoptotic signaling |
| GO:0006281 DNA repair | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: DNA repair transferred from mouse Trp53 (acts_upstream_of_or_within; mouse IGI PMID:35606358). p53 promotes repair largely by transactivating repair genes and enforcing arrest. Reason: Mouse Trp53 donor. p53 acts upstream of repair rather than performing repair chemistry; non-core. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0006302 double-strand break repair | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Double-strand break repair transferred from mouse Trp53 (mouse IMP PMID:17912366). p53-deficient germ cells accumulate unrepaired breaks. Reason: Mouse Trp53 donor. Upstream regulatory role in repair; non-core. Supporting Evidence: PMID:17912366 We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. |
| GO:0006355 regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (qualifier acts_upstream_of_or_within) of the reviewed regulation of DNA-templated transcription rows; mouse Trp53 donor. Reason: Mouse Trp53 (MGI:98834) donor. Generic parent of the specific Pol II regulation terms; non-core as for siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0006357 regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed regulation of transcription by RNA polymerase II row; mouse Trp53 donor with acts_upstream_of_or_within. Reason: Mouse Trp53 (MGI:98834) donor. Generic parent of the accepted positive/negative Pol II regulation terms; non-core as for sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0006606 protein import into nucleus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Protein import into nucleus transferred from mouse Trp53 (mouse IDA PMID:11799106), a study of cytosolic IkappaBalpha binding p53. Reason: Mouse Trp53 donor. p53 is the cargo whose nuclear entry is modulated by partners; it does not carry out nuclear import. Over-annotation of a regulatory interaction. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET Mouse IDA (PMID:11799106) on cytosolic IkappaBalpha binding p53; p53 is the cargo, not an agent of nuclear import. Supporting Evidence: PMID:11799106 Co-immunoprecipitation by anti-p53 antibody using Mv1Lu and other types of cells, as well as rat liver and spleen, revealed that a portion of cytosolic IkappaBalpha physically interacted with p53. |
| GO:0006915 apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Apoptotic process transferred from mouse Trp53 (acts_upstream_of_or_within; mouse IDA/IGI). Reason: Mouse Trp53 donor. p53 drives apoptosis mainly by transactivating pro-apoptotic genes; generic, non-core like the IEA sibling. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0006915 apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Apoptotic process (involved_in) transferred from mouse Trp53 (mouse IMP PMID:17434459). Reason: Mouse Trp53 donor. Generic apoptotic process; the specific p53-mediated intrinsic apoptosis terms are accepted elsewhere. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0006974 DNA damage response | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed DNA damage response rows; mouse Trp53 donor. Reason: Mouse Trp53 (MGI:98834) donor with multiple mouse IDA/IMP sources. DNA damage response is the core p53 pathway, consistent with siblings and core_functions. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Core pathway role: **DNA damage response** linking genotoxic or oncogenic stress to transcriptional reprogramming |
| GO:0006974 DNA damage response | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed DNA damage response rows; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor. Core pathway, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Core pathway role: **DNA damage response** linking genotoxic or oncogenic stress to transcriptional reprogramming |
| GO:0006979 response to oxidative stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the response to oxidative stress rows; mouse Trp53 donor (mouse IGI PMID:22726440, IMP PMID:17591690). Reason: Mouse Trp53 donor. p53 is activated by oxidative stress and relocates to mitochondria; non-core stress response, consistent with siblings. Supporting Evidence: UniProtKB:P10361 Translocates to mitochondria upon oxidative stress. UniProtKB:P10361 In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. |
| GO:0006983 ER overload response | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed ER overload response row; human TP53 donor (human IDA PMID:14744935). Reason: Human TP53 donor. Stress-context output; non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0007179 transforming growth factor beta receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Transforming growth factor beta receptor signaling pathway transferred from mouse Trp53 (mouse IGI PMID:18212064). Chromatin-bound p53 anchors activated Smads and mSin3A to mediate TGF-beta-dependent repression. Reason: Mouse Trp53 donor. The donor paper shows p53 acting as a Smad partner at target promoters; a real but context-specific role, non-core. Supporting Evidence: PMID:18212064 Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression. |
| GO:0007346 regulation of mitotic cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of mitotic cell cycle transferred from mouse Trp53 (mouse IDA PMID:17515607). Reason: Mouse Trp53 donor. p53 restrains cell division via transcriptional targets; non-core relative to the accepted DNA-damage checkpoint term. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0007369 gastrulation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Gastrulation transferred from mouse Trp53 (mouse IGI PMID:17000767, ribosomal protein S6 haploinsufficiency). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting; the developmental defect reflects inappropriate p53 activation (apoptosis/arrest) when negative regulators or ribosome/chromatin factors are lost, not a p53 role in executing gastrulation. The source describes a p53-dependent checkpoint triggered by ribosome insufficiency. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant (or sensitized) genotype in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:17000767 Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program. |
| GO:0007406 negative regulation of neuroblast proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of neuroblast proliferation transferred from mouse Trp53 (mouse IGI PMID:9608530). Reason: Mouse Trp53 donor. Antiproliferative output in a specific progenitor type; non-core. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0007417 central nervous system development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Central nervous system development transferred from mouse Trp53 (mouse IGI PMID:16199867, the Npm1 knockout study; MGI records the IGI partner as Lig4, MGI:1335098). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting. The donor paper shows that loss of nucleophosmin causes DNA damage, p53 activation, widespread apoptosis and mid-gestation lethality, and that a p53-null background rescues the apoptosis; the developmental defect therefore reflects inappropriate p53 activation when a genome-integrity factor is lost, not a p53 role in executing CNS development. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant genotype (PMID:16199867, Npm1-null with p53-null rescue of apoptosis) in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:16199867 Lack of NPM expression results in accumulation of DNA damage, activation of p53, widespread apoptosis, and mid-stage embryonic lethality. PMID:16199867 Transfer of the NPM mutation into a p53-null background rescued apoptosis in vivo and fibroblast proliferation in vitro. |
| GO:0007507 heart development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Heart development transferred from mouse Trp53 (mouse IGI PMID:22821713, Mdm2/Mdm4 compound mutants). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting; the developmental defect reflects inappropriate p53 activation (apoptosis/arrest) when negative regulators or ribosome/chromatin factors are lost, not a p53 role in executing heart development. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant (or sensitized) genotype in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:22821713 Synergistic regulation of p53 by Mdm2 and Mdm4 is critical in cardiac endocardial cushion morphogenesis during heart development. |
| GO:0008104 intracellular protein localization | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Donor-split of the reviewed intracellular protein localization row; human TP53 canonical plus isoform P04637-4 donors. Reason: Human TP53 donor (P04637, P04637-4). Generic, uninformative process term; same judgment as the sibling. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P04637 Β· human TP53 SUPPORTS SOURCE BUT NOT TARGET Human donor evidence (IDA PMID:16507995) is for a specific localisation event; the generic parent term conveys no function. UniProtKB:P04637-4 SUPPORTS SOURCE BUT NOT TARGET Isoform-level donor cited alongside the canonical entry; same specific localisation evidence, same granularity problem. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0008156 negative regulation of DNA replication | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of DNA replication transferred from mouse Trp53 (mouse IDA/IMP PMID:11884608). Reason: Mouse Trp53 donor. p53-dependent arrest restrains replication; downstream antiproliferative output, non-core. Supporting Evidence: UniProtKB:P10361 Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:30514107 CELF1/p53 axis: a sustained antiproliferative signal leading... | KEEP AS NON CORE | Summary: Qualifier-split (acts_upstream_of) of the reviewed IMP row from PMID:30514107 (rat TPN model, CELF1/p53 axis). Reason: Same rat experiment as the sibling IMP row; p53 mediates the antiproliferative signal in intestinal epithelium. Non-core. Supporting Evidence: PMID:30514107 Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). |
| GO:0008285 negative regulation of cell population proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed negative regulation of cell population proliferation rows; mouse Trp53 donor with multiple mouse IGI sources. Reason: Mouse Trp53 donor. Canonical antiproliferative output; non-core as for siblings. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0008285 negative regulation of cell population proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed negative regulation of cell population proliferation rows; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor. Non-core as for siblings. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. UniProtKB:P10361 regulates stress-induced TP53-dependent inhibition of cell proliferation. |
| GO:0009303 rRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: rRNA transcription transferred from mouse Trp53 (mouse IGI PMID:18809582, nucleophosmin study). Reason: Mouse Trp53 donor. The donor paper describes reduced rDNA transcription in NPM-null cells as an indirect ARF/p53-controlled effect; acceptable only as acts_upstream_of_or_within, non-core. Supporting Evidence: PMID:18809582 Moreover, the transcription of the rDNA locus is severely reduced in the absence of NPM, most likely through an indirect mechanism controlled by ARF and p53. |
| GO:0009410 response to xenobiotic stimulus | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the response to xenobiotic stimulus rows; mouse Trp53 donor (mouse IDA PMID:9098922). Reason: Mouse Trp53 donor. Genotoxic-stress response; non-core like siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0009411 response to UV | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the response to UV rows; mouse Trp53 donor (mouse IDA/IMP). Reason: Mouse Trp53 donor. DNA-damage-type stress response; non-core like siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0009651 response to salt stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Response to salt stress transferred from mouse Trp53 (mouse IGI PMID:16571598): p53 mediates renal dysplasia and apoptosis in salt-stressed bradykinin B2 receptor-null embryos. Reason: Mouse Trp53 donor. Context-specific stress response in a sensitized genotype; non-core. Supporting Evidence: PMID:16571598 Genetic analysis identified p53 as a mediator of the renal dysplasia in salt-stressed BdkrB2-/- mice, acting partly via repression of terminal epithelial differentiation genes. |
| GO:0009792 embryo development ending in birth or egg hatching | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Embryo development ending in birth or egg hatching transferred from mouse Trp53 (mouse IGI PMID:16702401, ASPP2 deletion). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in an ASPP2 x Trp53 genetic-interaction (IGI) experiment. The direction here is loss of function, not aberrant p53 activation - ASPP2-/- pups die before weaning, the lethality is enhanced in a p53+/- background and the double deletion is synthetic lethal, and the authors conclude ASPP2 shares overlapping function(s) with p53 in mouse development. Synthetic lethality shows that combined ASPP2/p53 dosage is necessary for survival (largely postnatal survival, which is outside embryo development proper); it does not identify any step of embryo development that p53 performs. Necessity evidence of this kind supports acts_upstream_of_or_within in mouse but is an over-annotation as a transferred developmental process term for rat Tp53. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse IGI from PMID:16702401 (ASPP2 deletion on a Trp53+/- or null background). Reduced p53 dose worsens ASPP2-/- lethality (synthetic lethality), indicating overlapping necessity of ASPP2 and p53 for survival; it supports p53 acting upstream of the phenotype in mouse, not participation in executing embryo development. Supporting Evidence: PMID:16702401 This postnatal lethality was significantly enhanced in p53+/- background and both deletions are synthetic lethal. PMID:16702401 ASPP2 is a haploinsufficient tumor suppressor that shares overlapping function(s) with p53 in mouse development and tumor suppression. |
| GO:0010165 response to X-ray | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the response to X-ray rows; mouse Trp53 donor. Reason: Mouse Trp53 donor. Radiation-induced DNA damage response; non-core like siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0010332 response to gamma radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the response to gamma radiation row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0010467 gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Gene expression transferred from mouse Trp53 (acts_upstream_of_or_within; mouse IMP PMID:21874018). Reason: Mouse Trp53 donor. The root gene-expression process says nothing beyond the specific Pol II transcription-regulation terms the gene already carries. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET Mouse experimental support is real but the generic gene-expression term adds nothing to the specific Pol II transcription-regulation terms. Supporting Evidence: UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Negative regulation of gene expression transferred from mouse Trp53 (mouse IGI PMID:18625840). Reason: Mouse Trp53 donor. Generic; p53 repression is captured by GO:0000122, consistent with treatment of the positive regulation of gene expression rows. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET Mouse experimental support is real but the generic gene-expression term adds nothing to the specific Pol II transcription-regulation terms. Supporting Evidence: UniProtKB:P10361 The nuclear export signal acts as a transcriptional repression domain. |
| GO:0010666 positive regulation of cardiac muscle cell apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of cardiac muscle cell apoptotic process transferred from mouse Trp53 (mouse IMP PMID:22044588). Reason: Mouse Trp53 donor. p53 aggravates ischemic cardiomyocyte loss; tissue-specific apoptotic output, non-core. Supporting Evidence: PMID:22044588 p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia. |
| GO:0017053 transcription repressor complex | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Transcription repressor complex transferred from human TP53 (human IPI PMID:18677113, PMID:8875929). Reason: Human TP53 donor. p53 assembles corepressor-containing complexes at some targets (e.g. with Smads and mSin3A); real but non-core relative to the accepted transcription regulator complex rows. Supporting Evidence: PMID:18212064 Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression. |
| GO:0021549 cerebellum development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cerebellum development transferred from mouse Trp53 (mouse IDA PMID:24013501). Reason: Mouse Trp53 donor (acts_upstream_of_or_within), from a single-locus Trp53(deltaCTD/deltaCTD) knock-in (Hamard et al. 2013) in which endogenous p53 is replaced by a mutant lacking the C-terminal 24 residues; there is no second mutated locus. Homozygotes die within 2 weeks with hematopoietic failure and impaired cerebellar development (absent vermis, thin EGL/IGL, disorganised Purkinje layer). The paper shows that the C terminus restrains p53 output in a tissue-specific way (hyperactive p53(deltaCTD) in bone marrow, thymus and spleen) and that in the cerebellum it regulates p53 function without changing p53 levels; the cerebellar defect is therefore the consequence of a dysregulated p53 allele, not evidence that p53 executes a step of cerebellar development. Supports acts_upstream_of_or_within in mouse; over-annotation as a transferred developmental process for rat Tp53. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse IDA from PMID:24013501, a single-locus Trp53(deltaCTD/deltaCTD) knock-in (not a compound mutant). Loss of the p53 C-terminal regulatory domain alters p53-dependent gene expression and disrupts cerebellar development; this places mis-regulated p53 upstream of the phenotype, not p53 as a participant in cerebellum development. Supporting Evidence: PMID:24013501 These Trp53(ΞCTD/ΞCTD) mice die within 2 wk post-partum with hematopoietic failure and impaired cerebellar development. PMID:24013501 This finding argues that the C-terminal domain regulates p53 functions in the cerebellum without interfering with its level of expression. PMID:24013501 First, in the bone marrow and thymus, the C terminus dampens p53 activity. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed DNA damage response, signal transduction by p53 class mediator row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Core p53 pathway, consistent with sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Core pathway role: **DNA damage response** linking genotoxic or oncogenic stress to transcriptional reprogramming UniProtKB:P10361 Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of TGF-beta receptor signaling pathway transferred from mouse Trp53 (mouse IMP PMID:15657445). Reason: Mouse Trp53 donor. The donor paper places p53 at a combined Smad/p53 element mediating TGF-beta-dependent repression; context-specific crosstalk, non-core. Supporting Evidence: PMID:15657445 Chromatin binding of p53 at the histone-acetylated SBE/p53RE region promotes the interaction of corepressor SnoN and HDAC complexes (and likely a histone methyltransferase), altering chromatin structure concomitantly with AFP repression. |
| GO:0031571 mitotic G1 DNA damage checkpoint signaling | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed mitotic G1 DNA damage checkpoint signaling row; mouse Trp53 donor (mouse IMP PMID:16107883). Reason: Mouse Trp53 donor. Core checkpoint output via CDKN1A, consistent with sibling and core_functions. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 transcriptionally activates CDKN1A/p21 and additional checkpoint mediators |
| GO:0031625 ubiquitin protein ligase binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed ubiquitin protein ligase binding rows; human TP53 donor. Reason: Human TP53 (UniProtKB:P04637) donor. p53 binds MDM2 and other E3 ligases that control its turnover; regulatory, non-core. Supporting Evidence: UniProtKB:P10361 Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. |
| GO:0033077 T cell differentiation in thymus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: T cell differentiation in thymus transferred from mouse Trp53 (mouse IGI PMID:16357222). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting; the developmental defect reflects inappropriate p53 activation (apoptosis/arrest) when negative regulators or ribosome/chromatin factors are lost, not a p53 role in executing thymocyte differentiation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant (or sensitized) genotype in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:16357222 Genetic inactivation of p53 tumor suppressor rescued development of S6-homozygous null thymocytes and proliferative defect of S6-heterozygous T cells. |
| GO:0033554 cellular response to stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to stress transferred from mouse Trp53 (mouse IGI PMID:26158450). Reason: Mouse Trp53 donor. True but very general; the specific DNA-damage terms carry the core claim. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0034103 regulation of tissue remodeling | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Regulation of tissue remodeling transferred from mouse Trp53 (mouse IMP PMID:22044588). Reason: Mouse Trp53 donor. Post-ischemic cardiac remodeling is an organ-level consequence of p53-driven cell death, not a process p53 executes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET Mouse IMP (PMID:22044588): post-ischemic cardiac remodeling is an organ-level consequence of p53-driven damage. Supporting Evidence: PMID:22044588 Inhibition of tumor suppressor p53 is cardioprotective against ischemic injury and provides resistance to subsequent cardiac remodeling. |
| GO:0034644 cellular response to UV | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed cellular response to UV row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0035033 histone deacetylase regulator activity | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Histone deacetylase regulator activity transferred from mouse Trp53 (mouse IDA PMID:15657445). The paper shows chromatin-bound p53 promotes recruitment of SnoN and HDAC complexes at the AFP promoter. Reason: Mouse Trp53 donor. Recruiting HDAC-containing corepressor complexes is not shown to modulate HDAC catalytic activity, which the term requires. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET Mouse IDA (PMID:15657445) shows p53-dependent recruitment of SnoN/HDAC corepressor complexes, not modulation of HDAC activity. Supporting Evidence: PMID:15657445 Chromatin binding of p53 at the histone-acetylated SBE/p53RE region promotes the interaction of corepressor SnoN and HDAC complexes (and likely a histone methyltransferase), altering chromatin structure concomitantly with AFP repression. |
| GO:0035264 multicellular organism growth | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Multicellular organism growth transferred from mouse Trp53 (mouse IGI PMID:17116431, PMID:17325035). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting; the developmental defect reflects inappropriate p53 activation (apoptosis/arrest) when negative regulators or ribosome/chromatin factors are lost, not a p53 role in executing organismal growth. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant (or sensitized) genotype in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:17325035 Here we show that deletion of p53 allows Gcn5(-/-) embryos to survive longer, but Gcn5(-/-) p53(-/-) embryos still die in midgestation. |
| GO:0035794 positive regulation of mitochondrial membrane permeability | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of mitochondrial membrane permeability transferred from mouse Trp53 (mouse IGI PMID:22726440). Matrix p53 binds cyclophilin D and opens the permeability transition pore. Reason: Mouse Trp53 donor. Transcription-independent, stress-induced role; real but non-core. Supporting Evidence: PMID:22726440 In response to oxidative stress and ischemia, p53 protein accumulates in the mitochondrial matrix and triggers PTP opening, mPT and necrosis by physical interaction with the critical PTP regulator CypD. UniProtKB:P10361 In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. |
| GO:0035861 site of double-strand break | ISO GO_REF:0000121 | UNDECIDED | Summary: Site of double-strand break transferred from mouse Trp53 (mouse IDA PMID:24550317). Reason: The cached donor paper (KDM4D recruitment to DNA damage sites) mentions only 'tumor protein P53 binding protein' (53BP1) foci and does not report p53 at break sites; possible symbol confusion with Trp53bp1 at the donor, which should be checked against the MGI curation. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE MISCITATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 UNRESOLVED Cached donor paper (PMID:24550317) mentions only 53BP1 ("tumor protein P53 binding protein") foci; possible Trp53bp1/Trp53 confusion to be checked at MGI. Supporting Evidence: PMID:24550317 Consistent with an upstream role in DDR, KDM4D knockdown disrupts the damage-induced recombinase Rad51 and tumor protein P53 binding protein foci formation. |
| GO:0042127 regulation of cell population proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of cell population proliferation transferred from mouse Trp53. Reason: Mouse Trp53 donor. Generic parent of the antiproliferative terms; non-core. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0042149 cellular response to glucose starvation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed cellular response to glucose starvation row; human TP53 donor (human IDA PMID:14744935). Reason: Human TP53 donor. Metabolic-stress output; non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 also regulates **metabolism, redox, autophagy, ferroptosis, and tumor microenvironment interactions** |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed GO:0042771 rows; mouse Trp53 donor with multiple mouse IMP/IGI sources. Reason: Mouse Trp53 donor. p53-mediated intrinsic apoptosis after DNA damage is core, consistent with siblings and core_functions. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed GO:0042771 rows; human TP53 donor. Reason: Human TP53 donor. Core, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed GO:0042771 rows; human TP53 donor (involved_in). Reason: Human TP53 donor. Core, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:0042981 regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed regulation of apoptotic process rows; human TP53 donor. Reason: Human TP53 donor. Generic parent; non-core like siblings. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0043065 positive regulation of apoptotic process | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed positive regulation of apoptotic process rows; mouse Trp53 donor. Reason: Mouse Trp53 donor. Consistent with sibling ACCEPT and core_functions. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed negative regulation of apoptotic process rows; mouse Trp53 donor (mouse IMP PMID:17912366, PMID:8183579). Reason: Mouse Trp53 donor. Context-dependent anti-apoptotic effect (e.g. germ cells); non-core like siblings. Supporting Evidence: PMID:17912366 We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed negative regulation of apoptotic process rows; human TP53 canonical plus isoform P04637-7 donors. Reason: Human TP53 donor (P04637, P04637-7). Context-dependent; non-core like siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 target programs and outcomes are **context-dependent** (tissue, cell type, stress type and magnitude), and can involve both transcriptional activation and repression |
| GO:0043504 mitochondrial DNA repair | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Mitochondrial DNA repair transferred from mouse Trp53 (mouse IMP PMID:24101517). Reason: Mouse Trp53 donor. p53 enters mitochondria via the CHCHD4 relay and contributes to mitochondrial genome integrity; non-core. Supporting Evidence: PMID:24101517 Here we report that the mammalian homolog of the yeast mitochondrial disulfide relay protein Mia40 (CHCHD4) is necessary for the respiratory-dependent translocation of p53 into the mitochondria. |
| GO:0043516 regulation of DNA damage response, signal transduction by p53 class mediator | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of DNA damage response, signal transduction by p53 class mediator, transferred from mouse Trp53 (mouse IGI PMID:21522133): a miR-29/Ppm1d loop feeds back on p53 activity. Reason: Mouse Trp53 donor. Autoregulatory feedback on its own pathway; non-core. Supporting Evidence: PMID:21522133 We have also found that miR-29 represses Ppm1d phosphatase, which in turn enhances p53 activity. |
| GO:0043523 regulation of neuron apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of neuron apoptotic process transferred from mouse Trp53 (mouse IGI PMID:15483136). Reason: Mouse Trp53 donor. Cell-type-specific apoptotic output; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0043525 positive regulation of neuron apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of neuron apoptotic process transferred from mouse Trp53 (multiple mouse IMP/IGI/IDA sources). Reason: Mouse Trp53 donor. Cell-type-specific pro-apoptotic output; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0045861 negative regulation of proteolysis | ISO GO_REF:0000121 | UNDECIDED | Summary: Negative regulation of proteolysis transferred from mouse Trp53 (mouse IMP PMID:23277542). Reason: The donor paper concerns c-Myc ubiquitylation and explicitly studies p53-independent c-Myc-induced apoptosis; the cached text does not show how Trp53 was assayed for proteolysis, so the transfer cannot be adjudicated. Propagation Review Root cause: UNRESOLVED Sources checked: MGI:MGI:98834 Β· mouse Trp53 UNRESOLVED Donor paper (PMID:23277542) studies p53-independent c-Myc-induced apoptosis; the Trp53 proteolysis assay is not evident in the cached text. Supporting Evidence: PMID:23277542 To further understand how c-Myc switches from an oncogenic protein to an apoptotic protein, we examined the mechanism of p53-independent c-Myc-induced apoptosis. |
| GO:0045892 negative regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed negative regulation of DNA-templated transcription rows; human TP53 donor. Reason: Human TP53 donor. Parent of GO:0000122; non-core like siblings. Supporting Evidence: UniProtKB:P10361 The nuclear export signal acts as a transcriptional repression domain. |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed positive regulation of DNA-templated transcription row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Parent of GO:0045944; non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0045930 negative regulation of mitotic cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of mitotic cell cycle transferred from mouse Trp53 (mouse IGI PMID:8612582). Reason: Mouse Trp53 donor. Antiproliferative output; non-core. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed GO:0045944 rows; mouse Trp53 donor with many mouse IDA/IMP sources. Reason: Mouse Trp53 donor. Core transcriptional activation, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed GO:0045944 rows; human TP53 donor. Reason: Human TP53 donor. Core, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed GO:0045944 rows; dog TP53 (RGD:12119451) donor. Reason: Dog TP53 donor curated at RGD. Core transcriptional activation, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed GO:0045944 rows; human TP53 donor. Reason: Human TP53 donor. Core, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** UniProtKB:P10361 Forms a complex with EP300 and NUPR1; this complex binds CDKN1A promoter leading to transcriptional induction of CDKN1A (By similarity). |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split of the reviewed GO:0045944 rows; human TP53 canonical plus isoform P04637-2 donors. Reason: Human TP53 donor (P04637, P04637-2). Core, consistent with siblings. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:0048144 fibroblast proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Fibroblast proliferation transferred from mouse Trp53 (mouse IGI PMID:26334721, Jmjd5 study). Reason: Mouse Trp53 donor (acts_upstream_of_or_within). p53 restrains fibroblast proliferation; non-core. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0048147 negative regulation of fibroblast proliferation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed negative regulation of fibroblast proliferation row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Non-core like sibling. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0048568 embryonic organ development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Embryonic organ development transferred from mouse Trp53 (mouse IGI PMID:17470788, PACT deletion). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting; the developmental defect reflects inappropriate p53 activation (apoptosis/arrest) when negative regulators or ribosome/chromatin factors are lost, not a p53 role in executing organ development. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant (or sensitized) genotype in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:17470788 PACT is a negative regulator of p53 and essential for cell growth and embryonic development. |
| GO:0050821 protein stabilization | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Protein stabilization transferred from mouse Trp53 (mouse IGI PMID:18625840, nucleophosmin and c-Myc turnover). Reason: Mouse Trp53 donor. In the donor study p53 acts genetically downstream of NPM loss; p53 does not stabilize proteins itself. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET Mouse IGI (PMID:18625840): p53 acts genetically downstream of NPM loss; it does not stabilize proteins. Supporting Evidence: PMID:18625840 In NPMβ/β embryos, cells proliferate more actively, accumulate DNA damage, and undergo p53-dependent apoptosis |
| GO:0051262 protein tetramerization | IEA GO_REF:0000002 | ACCEPT | Summary: Protein tetramerization (involved_in) from InterPro p53 tetramerization domain mappings; qualifier-split sibling of the reviewed IEA row. Reason: p53 forms homotetramers through its oligomerization domain, required for DNA binding; consistent with sibling ACCEPT. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md activated p53 forms tetramers; tetramerization is required for efficient DNA binding and full transactivation UniProtKB:P10361 Binds DNA as a homotetramer. |
| GO:0051276 chromosome organization | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Chromosome organization transferred from mouse Trp53 (mouse IGI PMID:17053789, PMID:17200209; POT1b telomere studies). Reason: Mouse Trp53 donor. In the donor studies p53 mediates senescence in response to telomere damage; genome instability in p53-deficient settings does not make p53 an agent of chromosome organization. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET Mouse IGI (PMID:17053789, PMID:17200209): p53 mediates senescence after telomere damage; not an agent of chromosome organization. Supporting Evidence: PMID:17053789 Overexpression of a mutant Pot1b allele that cannot bind telomeric DNA initiated a DNA damage response at telomeres that led to p53-dependent senescence. |
| GO:0051402 neuron apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Neuron apoptotic process transferred from mouse Trp53. Reason: Mouse Trp53 donor. Cell-type-specific apoptosis; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0051726 regulation of cell cycle | IMP PMID:30514107 CELF1/p53 axis: a sustained antiproliferative signal leading... | KEEP AS NON CORE | Summary: Qualifier-split (acts_upstream_of) of the reviewed IMP row from PMID:30514107. Reason: Same rat experiment as the sibling; non-core. Supporting Evidence: PMID:30514107 Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). |
| GO:0051726 regulation of cell cycle | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed regulation of cell cycle rows; mouse Trp53 donor. Reason: Mouse Trp53 donor. Non-core like siblings. Supporting Evidence: UniProtKB:P10361 Negatively regulates cell division by controlling expression of a set of genes required for this process. |
| GO:0060411 cardiac septum morphogenesis | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cardiac septum morphogenesis transferred from mouse Trp53 (mouse IGI PMID:22821713, Mdm2/Mdm4 compound mutants). Reason: acts_upstream_of_or_within phenotype from mouse Trp53 (MGI:98834) in a compound-mutant setting; the developmental defect reflects inappropriate p53 activation (apoptosis/arrest) when negative regulators or ribosome/chromatin factors are lost, not a p53 role in executing cardiac septum morphogenesis. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 SOURCE WEAK OR INFERRED Mouse phenotype from a compound-mutant (or sensitized) genotype in which p53 activation causes the defect; supports p53 acting upstream of the phenotype in mouse, not participation in the process. Supporting Evidence: PMID:22821713 Synergistic regulation of p53 by Mdm2 and Mdm4 is critical in cardiac endocardial cushion morphogenesis during heart development. |
| GO:0070243 regulation of thymocyte apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of thymocyte apoptotic process transferred from mouse Trp53 (mouse IGI PMID:17210642). Reason: Mouse Trp53 donor. Cell-type-specific apoptotic output; non-core like the positive regulation sibling. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0070245 positive regulation of thymocyte apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed positive regulation of thymocyte apoptotic process row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Non-core like sibling. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:0070266 necroptotic process | ISO GO_REF:0000121 | MODIFY | Summary: Necroptotic process transferred from mouse Trp53 (mouse IGI PMID:22726440). The donor paper shows p53-cyclophilin D-dependent permeability-transition necrosis. Reason: Mouse Trp53 donor. GO:0070266 is death-receptor/TLR-triggered necroptosis; the p53 mechanism is mitochondrial permeability transition-driven regulated necrosis, better captured by programmed necrotic cell death. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: MGI:MGI:98834 Β· mouse Trp53 SUPPORTS SOURCE BUT NOT TARGET Mouse IGI (PMID:22726440) shows p53-cyclophilin D permeability-transition necrosis, which is programmed necrosis but not death-receptor-triggered necroptosis. Proposed replacements: programmed necrotic cell death Supporting Evidence: PMID:22726440 In response to oxidative stress and ischemia, p53 protein accumulates in the mitochondrial matrix and triggers PTP opening, mPT and necrosis by physical interaction with the critical PTP regulator CypD. UniProtKB:P10361 In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. |
| GO:0071479 cellular response to ionizing radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed cellular response to ionizing radiation row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0071479 cellular response to ionizing radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed cellular response to ionizing radiation row; human TP53 donor. Reason: Human TP53 donor. Non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0071480 cellular response to gamma radiation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed cellular response to gamma radiation row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0071494 cellular response to UV-C | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cellular response to UV-C transferred from mouse Trp53 (mouse IGI PMID:24014029). Reason: Mouse Trp53 donor. DNA-damage stress response; non-core like the other UV rows. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Diverse cellular stresses (notably DNA damage) inhibit p53 ubiquitination, stabilize p53, and promote tetramer formation and DNA binding |
| GO:0072331 signal transduction by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed signal transduction by p53 class mediator row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Core pathway, consistent with sibling and core_functions. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md Core pathway role: **DNA damage response** linking genotoxic or oncogenic stress to transcriptional reprogramming |
| GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator | ISO GO_REF:0000121 | ACCEPT | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed intrinsic apoptotic signaling pathway by p53 class mediator row; mouse Trp53 donor. Reason: Mouse Trp53 donor. Core, consistent with sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 activates pro-apoptotic genes including **PUMA, BAX, NOXA** and can also contribute through non-transcriptional mitochondrial mechanisms |
| GO:1901525 negative regulation of mitophagy | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of mitophagy transferred from mouse Trp53 (mouse IMP PMID:22044588; p53-TIGAR axis). Reason: Mouse Trp53 donor. Indirect, via the p53 target TIGAR in ischemic heart; non-core. Supporting Evidence: PMID:22044588 p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia. |
| GO:1902108 regulation of mitochondrial membrane permeability involved in apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of mitochondrial membrane permeability involved in apoptotic process transferred from mouse Trp53 (mouse IGI PMID:14963330). Reason: Mouse Trp53 donor. p53 promotes MOMP via BCL-2-family proteins; non-core apoptotic mechanism. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 can trigger apoptosis through direct interactions with anti-apoptotic BCL-2 family members at mitochondria |
| GO:1902253 regulation of intrinsic apoptotic signaling pathway by p53 class mediator | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of intrinsic apoptotic signaling pathway by p53 class mediator transferred from mouse Trp53 (MGI cites PMID:17571083, a neuronal mutant-ubiquitin study that activated p53 cell death pathways). Reason: Mouse Trp53 donor. Regulation of its own apoptotic pathway in a neuronal stress context; non-core relative to the accepted p53-class intrinsic apoptosis terms. Supporting Evidence: PMID:17571083 Altered distribution of mitochondria was associated with activation of both the mitochondrial stress and p53 cell death pathways. |
| GO:1902749 regulation of cell cycle G2/M phase transition | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_negative_effect) of the reviewed regulation of cell cycle G2/M phase transition row; human TP53 donor (human IMP PMID:10962037). Reason: Human TP53 donor. G2/M arrest after DNA damage is a real p53 output; non-core like sibling. Supporting Evidence: UniProtKB:P10361 Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. |
| GO:1902895 positive regulation of miRNA transcription | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed positive regulation of miRNA transcription row; human TP53 donor. Reason: Human TP53 donor. p53 transactivates miRNA genes (e.g. miR-29); non-core like sibling. Supporting Evidence: PMID:21522133 Functional analysis revealed that this transcriptional activation of miR-29 is triggered in response to DNA damage and occurs in a p53-dependent manner |
| GO:1903799 negative regulation of miRNA processing | ISO GO_REF:0000121 | UNDECIDED | Summary: Negative regulation of miRNA processing transferred from mouse Trp53 (mouse IGI PMID:21522133). Reason: The cached full text of the donor paper reports p53-dependent transcriptional activation of miR-29 and a miR-29/Ppm1d feedback loop, but no effect on miRNA processing; the basis for the processing term cannot be found. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE MISCITATION Sources checked: MGI:MGI:98834 Β· mouse Trp53 UNRESOLVED Cached full text of the donor paper (PMID:21522133) reports transcriptional activation of miR-29, not regulation of miRNA processing. Supporting Evidence: PMID:21522133 Functional analysis revealed that this transcriptional activation of miR-29 is triggered in response to DNA damage and occurs in a p53-dependent manner |
| GO:1904024 negative regulation of glucose catabolic process to lactate via pyruvate | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of glucose catabolic process to lactate via pyruvate transferred from mouse Trp53 (mouse IMP PMID:20935145; p53-TIGAR in cardiomyocytes). Reason: Mouse Trp53 donor. Metabolic output via the transcriptional target TIGAR; non-core. Supporting Evidence: PMID:20935145 We investigated the role of p53 and its transcriptional target gene TP53-induced glycolysis and apoptosis regulator (TIGAR) in myocardial energy metabolism under conditions simulating ischemia that can lead to heart failure. |
| GO:1990144 intrinsic apoptotic signaling pathway in response to hypoxia | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Intrinsic apoptotic signaling pathway in response to hypoxia transferred from mouse Trp53 (mouse IMP PMID:20935145). Reason: Mouse Trp53 donor. Stress-specific apoptotic output; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:2000269 regulation of fibroblast apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of fibroblast apoptotic process transferred from mouse Trp53 (mouse IGI PMID:17116431). Reason: Mouse Trp53 donor. Cell-type-specific apoptotic output; non-core. Supporting Evidence: UniProtKB:P10361 Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Negative regulation of reactive oxygen species metabolic process transferred from mouse Trp53 (mouse IMP PMID:22044588). Reason: Mouse Trp53 donor. p53 has context-dependent pro- and anti-oxidant outputs (e.g. via TIGAR); non-core. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 also regulates **metabolism, redox, autophagy, ferroptosis, and tumor microenvironment interactions** |
| GO:2000772 regulation of cellular senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Regulation of cellular senescence transferred from mouse Trp53 (mouse IGI PMID:22904064). Reason: Mouse Trp53 donor. Senescence is a canonical p53 output; non-core like the other senescence rows. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
| GO:2000774 positive regulation of cellular senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split (acts_upstream_of_or_within) of the reviewed positive regulation of cellular senescence row; mouse Trp53 donor (mouse IGI PMID:17053789). Reason: Mouse Trp53 donor. Non-core like sibling. Supporting Evidence: PMID:17053789 Overexpression of a mutant Pot1b allele that cannot bind telomeric DNA initiated a DNA damage response at telomeres that led to p53-dependent senescence. |
| GO:2000774 positive regulation of cellular senescence | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Donor-split of the reviewed positive regulation of cellular senescence row; human TP53 donor. Reason: Human TP53 donor. Non-core like sibling. Supporting Evidence: file:rat/Tp53/Tp53-deep-research-falcon.md p53 binds p53 response elements in the genome and transcriptionally regulates gene programs that determine cell fate under stress, prominently including **cell-cycle arrest, DNA repair, apoptosis, and senescence** |
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Download this section (compressed HTML)Q: The mouse Trp53 somitogenesis IGI (partner Kat2a) is recorded with reference PMID:17320900, a Dlk1/Notch adipogenesis paper that does not mention p53 or somites, while the Gcn5/p53 compound-mutant paper PMID:17325035 reports that p53 loss lets Gcn5-null embryos develop somites. Is the recorded reference a data-entry error that MGI should correct, and does the intended evidence show p53 participating in somite formation or only acting upstream of presomitic-mesoderm survival?
Q: Which of the many tissue- and stimulus-specific p53 responses annotated by orthology (e.g. progesterone secretion, circadian behavior, outer hair cell apoptosis) reflect direct rat Tp53 functions versus transfer artifacts from other mammals?
Q: Is the reported in-vitro ATP-dependent DNA/DNA annealing and copper-ion-binding activity of p53 physiologically relevant in rat, or are these in-vitro artifacts that should not be annotated?
Q: Is the mouse Trp53 'site of double-strand break' IDA (PMID:24550317) a symbol confusion with Trp53bp1/53BP1? The cached paper reports only 53BP1 foci, so the rat ISO transfer should be checked against the MGI curation.
Q: What evidence underlies the mouse Trp53 annotations to negative regulation of miRNA processing (PMID:21522133) and negative regulation of proteolysis (PMID:23277542)? The cached texts describe p53-dependent miR-29 transcription and p53-independent c-Myc apoptosis respectively.
Q: How should the conflicting mouse Trp53 positive and NOT acts_upstream_of_or_within annotations to in utero embryonic development (both from compound-mutant studies) be reconciled before orthology transfer to rat?
Experiment: ChIP-seq for endogenous p53 in rat cells before and after a defined genotoxic stress (e.g. doxorubicin or ionizing radiation) to define the direct rat p53 cistrome and distinguish direct transcriptional targets from indirect/pleiotropic responses.
Type: ChIP-seq
Experiment: RNA-seq of rat cells with Tp53 knockout versus wild-type under basal and DNA-damage conditions to define the rat p53-dependent transcriptional program (arrest, apoptosis, senescence) and test which annotated downstream processes are p53-dependent in rat.
Type: RNA-seq
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