PMAIP1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001836 release of cytochrome c from mitochondria	IEA GO_REF:0000002	MODIFY	Summary: NOXA positively regulates cytochrome-c release rather than executing the release event itself. Reason: The InterPro mapping lands one step too deep. NOXA is a BH3-only regulator of the BCL2-family checkpoint that promotes MOMP and subsequent cytochrome-c release. Proposed replacements: positive regulation of release of cytochrome c from mitochondria
GO:0005515 protein binding	IPI PMID:15705586 Involvement of Noxa in cellular apoptotic responses to inter...	UNDECIDED	Summary: The dsRNA/virus paper reports a noncanonical NOXA/BAX interaction, but the full text is not locally available. Reason: Direct BAX binding is not part of the canonical NOXA mechanism; Willis et al. found that NOXA itself did not detectably bind BAX or BAK. Because the curated IntAct interaction comes from an abstract-only paper that explicitly reports a dsRNA-dependent NOXA/BAX interaction, leave this row unresolved until the full experiment can be inspected. Supporting Evidence: PMID:15901672 Noxa itself does not directly bind Bak or Bax
GO:0005515 protein binding	IPI PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not...	MODIFY	Summary: NOXA binds MCL1 through its BH3 helix and inhibits this pro-survival BCL2-family protein. Reason: This is a core NOXA/MCL1 interaction, but GO:0005515 is generic and GO:0051434 BH3 domain binding describes the MCL1 groove side. A NOXA-side pro-survival BCL2-family inhibitor activity is needed. Proposed replacements: pro-survival BCL2 family protein inhibitor activity Supporting Evidence: PMID:15901672 Noxa could bind to Mcl-1, displace Bak, and promote Mcl-1 degradation
GO:0005515 protein binding	IPI PMID:20085765 Noxa is necessary for hydrogen peroxide-induced caspase-depe...	UNDECIDED	Summary: Hydrogen peroxide induces NOXA and NOXA is required for mitochondrial apoptosis in Jurkat cells, but the exact MCL1 IPI is hidden behind an abstract-only cache. Reason: The row plausibly represents a NOXA/MCL1 inhibitory interaction, but the cached abstract does not expose the partner-specific pull-down needed to rewrite the generic contact to the proposed NOXA-side activity.
GO:0005515 protein binding	IPI PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce...	MODIFY	Summary: NOXA is sequestered by MCL1 in a BCL2-family complex in MCL1-dependent NSCLC cells. Reason: This MCL1 interaction is part of the same NOXA-side pro-survival BCL2-family inhibition mechanism, so it should not remain as GO:0005515 generic protein binding. Proposed replacements: pro-survival BCL2 family protein inhibitor activity
GO:0005515 protein binding	IPI PMID:21145489 The proapoptotic function of Noxa in human leukemia cells is...	UNDECIDED	Summary: The glucose/Cdk5 paper describes regulated NOXA-MCL1 association, but only the abstract is cached. Reason: The abstract supports a glucose-sensitive NOXA apoptosis switch, yet it does not expose the imported MCL1-isoform interaction. The row is likely a NOXA-side pro-survival BCL2-family inhibitor activity but should wait for full-text verification.
GO:0005515 protein binding	IPI PMID:21454712 Noxa/Bcl-2 protein interactions contribute to bortezomib res...	MODIFY	Summary: Full-length NOXA can bind BCL2 weakly in the bortezomib resistance context. Reason: Although MCL1 and BCL2A1 are the dominant physiological NOXA targets, PMID:21454712 supports lower-affinity full-length NOXA binding to the BCL2 groove. The row should be captured as the proposed NOXA-side inhibitor activity rather than GO:0005515. Proposed replacements: pro-survival BCL2 family protein inhibitor activity
GO:0005515 protein binding	IPI PMID:21454712 Noxa/Bcl-2 protein interactions contribute to bortezomib res...	MODIFY	Summary: Full-length NOXA can bind the canonical BCL2 isoform weakly in the bortezomib resistance context. Reason: This isoform-specific BCL2 row has the same interpretation as the parent BCL2 interaction: contextual, lower-affinity NOXA binding to a pro-survival BCL2-family groove. Proposed replacements: pro-survival BCL2 family protein inhibitor activity
GO:0005515 protein binding	IPI PMID:21454712 Noxa/Bcl-2 protein interactions contribute to bortezomib res...	MODIFY	Summary: NOXA binds MCL1 in bortezomib-treated lymphoid cells. Reason: The MCL1 interaction is core NOXA biology, but the row needs the proposed NOXA-side pro-survival BCL2-family inhibitor activity instead of GO:0005515. Proposed replacements: pro-survival BCL2 family protein inhibitor activity
GO:0005515 protein binding	IPI PMID:23563182 Polyubiquitination and proteasomal turnover controls the ant...	MODIFY	Summary: NOXA co-immunoprecipitates with the pro-survival BCL2-family protein BCL2L10/Bcl-B. Reason: The cited full text directly tests NOXA binding to Bcl-B, a pro-survival BCL2-family protein, and is best represented by the same proposed NOXA-side inhibitor activity. Proposed replacements: pro-survival BCL2 family protein inhibitor activity Supporting Evidence: PMID:23563182 Bim, Bik, Puma and Noxa interacted to a similar extent with WT and K/R mutant Bcl-B
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: The BioPlex row is an isolated high-throughput MCL1 interactor edge. Reason: Proteome-scale AP-MS does not by itself define NOXA's BH3 inhibitory molecular function, which is already supported by focused low-throughput MCL1 studies. Keeping this row as GO:0005515 would add only a redundant generic contact.
GO:0005634 nucleus	IDA PMID:12879012 Noxa in colorectal cancer: a study on DNA, mRNA and protein ...	UNDECIDED	Summary: The colorectal cancer paper reports NOXA protein expression, but the exact nuclear localization evidence is unavailable. Reason: NOXA is primarily a mitochondrial/cytosolic BH3-only protein. The cached abstract describes immunohistochemistry in tumors without exposing the staining pattern that led to a nucleus annotation, so this experimental row should remain unresolved.
GO:0005739 mitochondrion	EXP PMID:17374615 Functional linkage between NOXA and Bim in mitochondrial apo...	ACCEPT	Summary: NOXA localizes to mitochondria as part of BH3-dependent apoptotic signaling. Reason: Mitochondrial localization is the established site where NOXA engages pro-survival BCL2-family proteins and licenses downstream mitochondrial permeabilization.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: PMAIP1 was recovered in a high-confidence human mitochondrial proteome dataset. Reason: The high-throughput localization agrees with repeated focused NOXA mitochondrial localization studies and with the core mitochondrial BCL2-family mechanism. Supporting Evidence: PMID:34800366 We defined a human mitochondrial high-confidence proteome MitoCoP
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: The eutherian PMAIP1 PAINT node asserts mitochondrial localization. Reason: PANTHER PTHR14299/PTN000370924 only propagates mitochondrial localization; that placement matches human and mouse NOXA evidence and there is no target-specific evidence of loss.
GO:0005739 mitochondrion	IDA PMID:14500711 The molecular mechanism of Noxa-induced mitochondrial dysfun...	ACCEPT	Summary: NOXA localizes to mitochondria as part of BH3-dependent apoptotic signaling. Reason: Mitochondrial localization is the established site where NOXA engages pro-survival BCL2-family proteins and licenses downstream mitochondrial permeabilization.
GO:0005739 mitochondrion	IDA PMID:15102863 BOK and NOXA are essential mediators of p53-dependent apopto...	ACCEPT	Summary: NOXA localizes to mitochondria as part of BH3-dependent apoptotic signaling. Reason: Mitochondrial localization is the established site where NOXA engages pro-survival BCL2-family proteins and licenses downstream mitochondrial permeabilization.
GO:0005739 mitochondrion	IDA PMID:15705586 Involvement of Noxa in cellular apoptotic responses to inter...	ACCEPT	Summary: NOXA localizes to mitochondria as part of BH3-dependent apoptotic signaling. Reason: Mitochondrial localization is the established site where NOXA engages pro-survival BCL2-family proteins and licenses downstream mitochondrial permeabilization.
GO:0005739 mitochondrion	IDA PMID:21145489 The proapoptotic function of Noxa in human leukemia cells is...	ACCEPT	Summary: NOXA localizes to mitochondria as part of BH3-dependent apoptotic signaling. Reason: Mitochondrial localization is the established site where NOXA engages pro-survival BCL2-family proteins and licenses downstream mitochondrial permeabilization.
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: NOXA localizes to mitochondria as part of BH3-dependent apoptotic signaling. Reason: Mitochondrial localization is the established site where NOXA engages pro-survival BCL2-family proteins and licenses downstream mitochondrial permeabilization.
GO:0005741 mitochondrial outer membrane	TAS Reactome:R-HSA-140216	ACCEPT	Summary: Reactome places NOXA at the mitochondrial outer membrane during its translocation step. Reason: The mitochondrial outer membrane is the specific site where BH3-only NOXA engages pro-survival BCL2-family proteins.
GO:0005741 mitochondrial outer membrane	TAS Reactome:R-HSA-508162	ACCEPT	Summary: Reactome places NOXA at the BCL2-family mitochondrial outer-membrane compartment. Reason: The Reactome BCL-XL event is weak for NOXA partner selectivity, because NOXA is principally MCL1/BCL2A1-selective, but this row asserts only the mitochondrial outer-membrane compartment and that localization is correct.
GO:0005829 cytosol	IDA PMID:15705586 Involvement of Noxa in cellular apoptotic responses to inter...	ACCEPT	Summary: NOXA can be detected in cytosol as well as mitochondria before or during apoptotic signaling. Reason: Cytosolic NOXA is compatible with subsequent mitochondrial targeting in dsRNA/virus-induced apoptosis.
GO:0005829 cytosol	IDA PMID:21145489 The proapoptotic function of Noxa in human leukemia cells is...	ACCEPT	Summary: Glucose-regulated phosphorylation can sequester NOXA in the cytosol. Reason: Cytosol is a supported secondary localization for inhibited, phosphorylated NOXA in proliferating leukemia cells.
GO:0005829 cytosol	TAS Reactome:R-HSA-140214	ACCEPT	Summary: Cytosol from the Reactome reaction for TP53-stimulated PMAIP1 expression; the same location is accepted for NOXA on direct-assay rows. Reason: Cytosol is accepted for NOXA in this review on two direct-assay rows and on the Reactome row for its translocation to mitochondria, so the location stands on this row as well. This Reactome row derives from the reaction in which TP53 stimulates PMAIP1 expression, whose protein product is placed in the cytosol, rather than from a localization experiment; that limits its evidence but does not change the claim. Rows that share a term are judged alike, so the row is accepted with the others rather than removed.
GO:0005829 cytosol	TAS Reactome:R-HSA-140216	ACCEPT	Summary: Reactome correctly models cytosolic NOXA as the source pool for mitochondrial translocation. Reason: Cytosolic NOXA before mitochondrial targeting is compatible with the translocation-to-mitochondria event.
GO:0005829 cytosol	TAS Reactome:R-HSA-140217	ACCEPT	Summary: Cytosol from the Reactome reaction for E2F1-driven PMAIP1 transcription; the same location is accepted for NOXA on direct-assay rows. Reason: Cytosol is accepted for NOXA in this review on two direct-assay rows and on the Reactome row for its translocation to mitochondria, so the location stands on this row as well. This Reactome row derives from the reaction in which E2F1 activates PMAIP1 transcription, whose protein product is placed in the cytosol, rather than from a localization experiment; that limits its evidence but does not change the claim. Rows that share a term are judged alike, so the row is accepted with the others rather than removed.
GO:0006915 apoptotic process	IEA GO_REF:0000002	MODIFY	Summary: NOXA positively regulates apoptotic MOMP, making top-level apoptotic process too broad. Reason: The InterPro2GO row has the right direction but should be tightened to the mitochondrial BCL2-family checkpoint controlled by NOXA. Proposed replacements: positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:0006915 apoptotic process	IMP PMID:17599062 CDIP, a novel pro-apoptotic gene, regulates TNFalpha-mediate...	MODIFY	Summary: The CDIP paper uses NOXA knockdown as a peripheral comparator in p53-mediated apoptosis. Reason: NOXA is a bona fide apoptotic regulator, but the human IMP row overstates this specific CDIP source, which is focused on a p53-CDIP-TNF-alpha pathway rather than PMAIP1 as the proximal assayed effector. Proposed replacements: positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:0006974 DNA damage response	IEA GO_REF:0000002	MODIFY	Summary: NOXA is a downstream p53-induced apoptosis effector, not a DNA-damage response protein. Reason: DNA damage induces TP53-dependent PMAIP1 transcription; the NOXA protein then acts at the mitochondrial intrinsic-apoptosis checkpoint. The p53/DNA-damage intrinsic-apoptotic descendant captures that biology more precisely. Proposed replacements: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0010498 proteasomal protein catabolic process	IDA PMID:15901672 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not...	MODIFY	Summary: NOXA binding can promote proteasomal degradation of MCL1. Reason: NOXA promotes MCL1 turnover rather than executing proteasomal degradation itself, so the positive-regulation term is more precise than GO:0010498. Proposed replacements: positive regulation of proteasomal protein catabolic process Supporting Evidence: PMID:15901672 Noxa could bind to Mcl-1, displace Bak, and promote Mcl-1 degradation PMID:17389404 Noxa is a BH3-only protein that can bind and trigger proteasome-mediated Mcl-1 degradation
GO:0010907 positive regulation of glucose metabolic process	IDA PMID:21145489 The proapoptotic function of Noxa in human leukemia cells is...	MARK AS OVER ANNOTATED	Summary: The glucose-metabolism row reflects a specialized growth-state effect of phosphorylated NOXA. Reason: PMID:21145489 suggests that NOXA may alter glucose consumption in hematopoietic cancer cells, but this is a contextual effect rather than NOXA's portable apoptotic function.
GO:0010917 negative regulation of mitochondrial membrane potential	ISS PMID:14699081 BH3-only protein Noxa is a mediator of hypoxic cell death in...	MODIFY	Summary: NOXA promotes mitochondrial permeabilization; loss of membrane potential is a downstream readout. Reason: Mouse-to-human transfer to a membrane-potential term is less precise than the apoptotic MOMP regulation carried out by BH3-only NOXA upstream of cytochrome-c release. Proposed replacements: positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:0042149 cellular response to glucose starvation	IMP PMID:21145489 The proapoptotic function of Noxa in human leukemia cells is...	MARK AS OVER ANNOTATED	Summary: Glucose starvation controls NOXA phosphorylation and pro-apoptotic activity in leukemia cells. Reason: The source supports a glucose-stress context around NOXA activity, but PMAIP1 is not a general executor of the cellular response to glucose starvation.
GO:0043029 T cell homeostasis	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: The T-cell homeostasis row is a mouse immune-physiology transfer onto human PMAIP1. Reason: NOXA-dependent apoptosis can shape mouse T-cell homeostasis, but this is a physiological outcome of the mitochondrial checkpoint and not a core human NOXA process annotation.
GO:0043065 positive regulation of apoptotic process	IDA PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce...	MODIFY	Summary: NOXA promotes apoptosis in the MCL1/BIM/BAK mitochondrial checkpoint. Reason: ComplexPortal correctly captures the MCL1-PMAIP1 complex, but the process row should be narrowed from generic positive apoptotic regulation to apoptotic MOMP regulation. Proposed replacements: positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:0043065 positive regulation of apoptotic process	IDA PMID:21145489 The proapoptotic function of Noxa in human leukemia cells is...	MARK AS OVER ANNOTATED	Summary: Glucose and Cdk5 tune NOXA pro-apoptotic activity in leukemia cells. Reason: The broad positive-apoptosis row is a contextual glucose-stress annotation from an abstract-only source; without the full figure, it should not be generalized into core PMAIP1 biology.
GO:0043065 positive regulation of apoptotic process	IEA GO_REF:0000002	MODIFY	Summary: InterPro2GO maps PMAIP1 to a generic apoptosis-regulation parent. Reason: NOXA directly acts at the mitochondrial BCL2-family checkpoint, so positive regulation of apoptotic MOMP is more informative than broad positive regulation of apoptotic process. Proposed replacements: positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:0043065 positive regulation of apoptotic process	IMP PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h...	UNDECIDED	Summary: NOXA likely participates in the BH3-ligand mechanism assayed in PMID:17289999, but the local cache lacks the full text. Reason: The abstract establishes the general indirect-activation model but does not expose the exact NOXA perturbation imported into GOA, so the row should wait for full-text inspection before a more specific MOMP replacement is asserted.
GO:0043065 positive regulation of apoptotic process	IMP PMID:21525171 Bortezomib primes glioblastoma, including glioblastoma stem ...	UNDECIDED	Summary: Mutant-phenotype annotation from a study of bortezomib and TRAIL in glioblastoma (PMID:21525171; abstract only), whose abstract reports that Noxa silencing did not protect cells. Reason: The pro-apoptotic role of NOXA is not in question and is recognized on the other rows for this term. This row cites a study of bortezomib and TRAIL in glioblastoma whose abstract reports that silencing of Noxa did not confer protection, whereas knockdown of Bid did, so the abstract does not support a mutant-phenotype annotation for NOXA; only the abstract is available, and what the curator relied on in the full text cannot be checked. The row is therefore left undecided, like the other mutant-phenotype row for this term, rather than removed. Supporting Evidence: PMID:21525171 silencing of Noxa, which is also upregulated by bortezomib, does not confer protection
GO:0043331 response to dsRNA	IDA PMID:15705586 Involvement of Noxa in cellular apoptotic responses to inter...	MARK AS OVER ANNOTATED	Summary: NOXA is induced downstream of dsRNA and contributes to apoptosis in that innate-stimulus context. Reason: NOXA acts as a BH3-only mitochondrial effector after dsRNA/IFN/virus induction; annotating it to the broad response-to-dsRNA process overstates that stimulus-response role.
GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator	IMP PMID:15102863 BOK and NOXA are essential mediators of p53-dependent apopto...	MODIFY	Summary: NOXA is a p53-induced apoptotic effector downstream of DNA damage, not a positive regulator of p53 signaling. Reason: PMAIP1 transcription is induced by p53 after DNA damage; the NOXA protein then promotes mitochondrial intrinsic apoptosis. It should not be curated as feeding positively into the upstream p53 signal-transduction pathway. Proposed replacements: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0046902 regulation of mitochondrial membrane permeability	IDA PMID:14500711 The molecular mechanism of Noxa-induced mitochondrial dysfun...	MODIFY	Summary: NOXA regulates mitochondrial permeabilization through the apoptotic BCL2-family checkpoint. Reason: GO:0046902 is broad and polarity-free; NOXA specifically promotes apoptotic mitochondrial outer-membrane permeabilization. Proposed replacements: positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:0051607 defense response to virus	IDA PMID:15705586 Involvement of Noxa in cellular apoptotic responses to inter...	MARK AS OVER ANNOTATED	Summary: NOXA contributes to virus-induced apoptosis as a downstream BH3-only effector. Reason: The evidence places NOXA in apoptosis induced by IFN, dsRNA, and virus, but PMAIP1 itself is not a direct antiviral effector pathway component.
GO:0071456 cellular response to hypoxia	IEP PMID:14699081 BH3-only protein Noxa is a mediator of hypoxic cell death in...	MARK AS OVER ANNOTATED	Summary: HIF1A-dependent hypoxia can induce PMAIP1 and route NOXA into mitochondrial apoptosis. Reason: The source supports NOXA as a hypoxia-induced apoptotic effector, but the protein's direct role is still at the BCL2-family MOMP checkpoint rather than in the broad cellular response to hypoxia.
GO:0071456 cellular response to hypoxia	IEP PMID:20810912 Hypoxia downregulates p53 but induces apoptosis and enhances...	MARK AS OVER ANNOTATED	Summary: Expression-pattern annotation citing a study of hypoxic syncytiotrophoblasts (PMID:20810912) in which noxa mRNA was unchanged or slightly reduced; treated like the other row for this term. Reason: The same term is marked as an over-annotation on the other expression-pattern row of this review, which rests on induction of NOXA by hypoxia-inducible factor, and the claim is the same here. This row cites a study of hypoxic syncytiotrophoblasts whose full text reports that noxa mRNA was unchanged or slightly reduced, so the reference does not support the annotation; that is a problem of this row's source and is recorded as such. Rows that share a term are judged alike, so the row is marked rather than removed. Supporting Evidence: PMID:20810912 mRNA levels of both of these genes were unchanged or slightly reduced
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator	IMP PMID:15102863 BOK and NOXA are essential mediators of p53-dependent apopto...	MODIFY	Summary: NOXA mediates p53-dependent intrinsic apoptosis after DNA damage. Reason: The row should be tightened to the DNA-damage response branch of p53-class intrinsic apoptotic signaling. Proposed replacements: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0072593 reactive oxygen species metabolic process	IDA PMID:14699081 BH3-only protein Noxa is a mediator of hypoxic cell death in...	MARK AS OVER ANNOTATED	Summary: ROS is a downstream component or readout of NOXA-dependent hypoxic death, not a PMAIP1 metabolic activity. Reason: The cited study shows that reactive oxygen species and the resulting cytochrome c release participate in NOXA-mediated hypoxic cell death (PMID:14699081), so the row records a real measurement. Reactive oxygen species are there a downstream component and readout of the death pathway that NOXA initiates; NOXA is a BH3-only regulator and performs no step of reactive oxygen species metabolism. The term annotates a consequence of NOXA action to NOXA and is marked as an over-annotation rather than removed.
GO:0090200 positive regulation of release of cytochrome c from mitochondria	IDA PMID:14500711 The molecular mechanism of Noxa-induced mitochondrial dysfun...	ACCEPT	Summary: NOXA promotes cytochrome-c release from mitochondria. Reason: This term is appropriately regulatory for the BH3-only protein that licenses mitochondrial cytochrome-c efflux.
GO:0090200 positive regulation of release of cytochrome c from mitochondria	IDA PMID:14699081 BH3-only protein Noxa is a mediator of hypoxic cell death in...	ACCEPT	Summary: NOXA promotes cytochrome-c release during hypoxic mitochondrial apoptosis. Reason: The full text links NOXA knockdown to reduced cytochrome-c release in hypoxia, matching this regulatory term. Supporting Evidence: PMID:14699081 Taken together, our data indicate that Noxa induced ROS-dependent cytochrome c release and caspase-3 activation.
GO:0090200 positive regulation of release of cytochrome c from mitochondria	IDA PMID:15705586 Involvement of Noxa in cellular apoptotic responses to inter...	ACCEPT	Summary: NOXA promotes cytochrome-c release downstream of mitochondrial BCL2-family control. Reason: Positive regulation of cytochrome-c release is appropriately scoped: NOXA inhibits MCL1 and related pro-survival proteins upstream of the BAX/BAK pore that releases cytochrome c.
GO:0090200 positive regulation of release of cytochrome c from mitochondria	IMP PMID:15705586 Involvement of Noxa in cellular apoptotic responses to inter...	ACCEPT	Summary: NOXA promotes cytochrome-c release downstream of mitochondrial BCL2-family control. Reason: Positive regulation of cytochrome-c release is appropriately scoped: NOXA inhibits MCL1 and related pro-survival proteins upstream of the BAX/BAK pore that releases cytochrome c.
GO:0090200 positive regulation of release of cytochrome c from mitochondria	IMP PMID:17289999 Apoptosis initiated when BH3 ligands engage multiple Bcl-2 h...	UNDECIDED	Summary: NOXA likely drives cytochrome-c release through pro-survival BCL2-family inhibition in PMID:17289999, but the exact imported experiment is hidden. Reason: The cached abstract does not expose the NOXA-specific IMP behind this row. The mechanism is plausible, but a full-text check is needed before accepting or tightening the annotation.
GO:0097136 Bcl-2 family protein complex	IPI PMID:21132008 Mcl-1 is critical for survival in a subgroup of non-small-ce...	ACCEPT	Summary: NOXA is a component of MCL1-containing BCL2-family protein complexes. Reason: MCL1-PMAIP1 is a bona fide BCL2-family complex in which NOXA binds the MCL1 groove through its BH3 helix.
GO:0097193 intrinsic apoptotic signaling pathway	IDA PMID:14500711 The molecular mechanism of Noxa-induced mitochondrial dysfun...	ACCEPT	Summary: NOXA is involved in intrinsic apoptotic signaling upstream of mitochondrial cytochrome-c release. Reason: Although a MOMP regulatory term is more mechanistic for many rows, this broad intrinsic-apoptosis term is still correct for BH3-only NOXA.
GO:1902043 positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	IDA PMID:15705586 Involvement of Noxa in cellular apoptotic responses to inter...	MODIFY	Summary: The IFN/dsRNA/virus evidence supports mitochondrial cytochrome-c release, not death-domain receptor signaling. Reason: PMID:15705586 did not assay a FAS/TNF/TRAIL death-domain receptor pathway; the supported apoptosis event is enhanced mitochondrial cytochrome-c release. Proposed replacements: positive regulation of release of cytochrome c from mitochondria
GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	TAS PMID:22013210 The unfolded protein response: integrating stress signals th...	UNDECIDED	Summary: The cached IRE1/UPR review does not expose evidence for NOXA in ER-stress intrinsic apoptosis. Reason: Because the source is a review and the abstract does not mention NOXA, this TAS row should not be accepted without checking the cited primary evidence.
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway	IDA PMID:21454712 Noxa/Bcl-2 protein interactions contribute to bortezomib res...	MODIFY	Summary: NOXA/BCL2-family interactions promote mitochondrial intrinsic apoptotic signaling in bortezomib-treated lymphoid cells. Reason: The evidence is proximal to the mitochondrial checkpoint; positive regulation of apoptotic MOMP is more mechanistic than the broad positive regulation of intrinsic apoptotic signaling term. Proposed replacements: positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway

Gene Description

Proposed New Ontology Terms

pro-survival BCL2 family protein inhibitor activity

Existing Annotations Review

Core Functions

NOXA uses its BH3 helix to bind and inhibit pro-survival BCL2-family proteins, most prominently MCL1 and BCL2A1, derepressing BAX/BAK-dependent mitochondrial outer-membrane permeabilization and cytochrome-c release.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

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