cep-1 encodes the single C. elegans p53-family transcription factor. CEP-1 localizes to germline nuclei and uses its p53-like DNA-binding domain and dimeric C-terminal oligomerization/SAM domain to activate RNA polymerase II target genes. Its best-established apoptotic role is in the germline DNA-damage pathway, where CEP-1 induces the BH3-only genes egl-1 and ced-13 upstream of the CED-9/CED-4/CED-3 intrinsic apoptosis module. CEP-1 also regulates additional development, stress, and lifespan outputs, including fasn-1 and phg-1, and its DNA-damage apoptotic output is restrained by GLD-1-dependent translational repression and by a PRMT-5/CBP-1 complex that represses CEP-1 transcriptional activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001666 response to hypoxia | IMP PMID:11557844 Caenorhabditis elegans p53: role in apoptosis, meiosis, and ... | KEEP AS NON CORE | Summary: CEP-1 contributes to organismal survival under hypoxic stress, a somatic stress output outside the core germline apoptosis pathway. Reason: The cached Science abstract reports hypoxia hypersensitivity in cep-1 mutants and summarizes a somatic stress-response role. Because the full text is not cached, the precise proximal target is unclear, but the broad response-to-hypoxia annotation can be retained as non-core. Supporting Evidence: PMID:11557844 hypersensitivity to hypoxia-induced lethality PMID:11557844 C. elegans p53 mediates multiple stress responses in the soma |
| GO:0003677 DNA binding | IDA PMID:15242600 Structural differences in the DNA binding domains of human p... | MODIFY | Summary: DNA binding is correct but less informative than CEP-1 sequence-specific transcription activator activity. Reason: CEP-1 is a nuclear p53-family DNA-binding transcription factor. Its p53-like DNA-binding domain recognizes p53 response elements, and the better molecular-function term is the RNA polymerase II-specific transcription activator activity. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:15242600 recognize essentially identical DNA sequences despite poor sequence similarity PMID:11696333 transcription factor and is able to activate a transcriptional reporter PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | MODIFY | Summary: DNA binding is correct but less informative than CEP-1 sequence-specific transcription activator activity. Reason: CEP-1 is a nuclear p53-family DNA-binding transcription factor. Its p53-like DNA-binding domain recognizes p53 response elements, and the better molecular-function term is the RNA polymerase II-specific transcription activator activity. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:15242600 recognize essentially identical DNA sequences despite poor sequence similarity PMID:11696333 transcription factor and is able to activate a transcriptional reporter PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:11696333 The C. elegans homolog of the p53 tumor suppressor is requir... | MODIFY | Summary: CEP-1 is an RNA polymerase II transcription activator, so the broad DNA-binding transcription factor term should be made more specific. Reason: The original and profiling studies place CEP-1 as a p53-family transcriptional activator that induces a small set of direct RNA polymerase II targets, including the BH3-only apoptosis genes egl-1 and ced-13 and the fatty-acid synthase gene fasn-1. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:11696333 transcription factor and is able to activate a transcriptional reporter PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo PMID:18627611 Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:18627611 Transcriptional profiling in C. elegans suggests DNA damage ... | MODIFY | Summary: CEP-1 is an RNA polymerase II transcription activator, so the broad DNA-binding transcription factor term should be made more specific. Reason: The original and profiling studies place CEP-1 as a p53-family transcriptional activator that induces a small set of direct RNA polymerase II targets, including the BH3-only apoptosis genes egl-1 and ced-13 and the fatty-acid synthase gene fasn-1. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:11696333 transcription factor and is able to activate a transcriptional reporter PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo PMID:18627611 Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | MODIFY | Summary: CEP-1 is an RNA polymerase II transcription activator, so the broad DNA-binding transcription factor term should be made more specific. Reason: The original and profiling studies place CEP-1 as a p53-family transcriptional activator that induces a small set of direct RNA polymerase II targets, including the BH3-only apoptosis genes egl-1 and ced-13 and the fatty-acid synthase gene fasn-1. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:11696333 transcription factor and is able to activate a transcriptional reporter PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo PMID:18627611 Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene |
| GO:0005634 nucleus | IDA PMID:11557844 Caenorhabditis elegans p53: role in apoptosis, meiosis, and ... | ACCEPT | Summary: CEP-1 is a nuclear transcription factor. Reason: The direct and electronic nucleus rows are consistent with CEP-1 acting in germ-cell nuclei as a p53-family DNA-binding transcription factor. Supporting Evidence: PMID:20970339 CEP-1 also localizes to the nucleoplasm in late pachytene nuclei of the male germ line PMID:11696333 transcription factor and is able to activate a transcriptional reporter |
| GO:0005634 nucleus | IDA PMID:20970339 Meiotic errors activate checkpoints that improve gamete qual... | ACCEPT | Summary: CEP-1 is a nuclear transcription factor. Reason: The direct and electronic nucleus rows are consistent with CEP-1 acting in germ-cell nuclei as a p53-family DNA-binding transcription factor. Supporting Evidence: PMID:20970339 CEP-1 also localizes to the nucleoplasm in late pachytene nuclei of the male germ line PMID:11696333 transcription factor and is able to activate a transcriptional reporter |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: CEP-1 is a nuclear transcription factor. Reason: The direct and electronic nucleus rows are consistent with CEP-1 acting in germ-cell nuclei as a p53-family DNA-binding transcription factor. Supporting Evidence: PMID:20970339 CEP-1 also localizes to the nucleoplasm in late pachytene nuclei of the male germ line PMID:11696333 transcription factor and is able to activate a transcriptional reporter |
| GO:0005654 nucleoplasm | IDA PMID:15707894 Translational repression of C. elegans p53 by GLD-1 regulate... | ACCEPT | Summary: The nucleoplasm placement is consistent with full-text imaging of CEP-1 in germ-cell nuclei. Reason: Although the original GLD-1 paper is abstract-only in the local cache, independent full-text imaging in male germ lines places CEP-1 in the nucleoplasm of late pachytene nuclei. Supporting Evidence: PMID:20970339 CEP-1 also localizes to the nucleoplasm in late pachytene nuclei of the male germ line |
| GO:0005730 nucleolus | IDA PMID:11557844 Caenorhabditis elegans p53: role in apoptosis, meiosis, and ... | UNDECIDED | Summary: The old WormBase nucleolus row may come from CEP-1::GFP imaging, but the precise nucleolar claim cannot be checked from the cached abstract. Reason: The supporting paper is abstract-only locally and its abstract establishes broad embryo expression and stress phenotypes rather than a nucleolar localization. Keep this for a WormBase or image-level recheck. |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:11696333 The C. elegans homolog of the p53 tumor suppressor is requir... | MODIFY | Summary: Regulation of transcription is correct but should be narrowed to positive regulation of RNA polymerase II transcription. Reason: CEP-1 acts as a p53-family transcriptional activator of Pol II target genes; the existing process term is a broad parent of the more informative positive-regulation term already supported by direct fasn-1 target evidence. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:11696333 transcription factor and is able to activate a transcriptional reporter PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: Regulation of transcription is correct but should be narrowed to positive regulation of RNA polymerase II transcription. Reason: CEP-1 acts as a p53-family transcriptional activator of Pol II target genes; the existing process term is a broad parent of the more informative positive-regulation term already supported by direct fasn-1 target evidence. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:11696333 transcription factor and is able to activate a transcriptional reporter PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo |
| GO:0006979 response to oxidative stress | IMP PMID:18836529 A novel role for the SMG-1 kinase in lifespan and oxidative ... | MARK AS OVER ANNOTATED | Summary: CEP-1 is genetically required for the oxidative-stress resistance caused by smg-1 inactivation, but the evidence is an epistasis endpoint. Reason: The SMG-1 study showed that smg-1 inactivation confers paraquat resistance in a daf-18-, daf-16-, and cep-1-dependent pathway. That places CEP-1 in the longevity/stress-resistance network but does not show that CEP-1 itself directly executes an oxidative-stress response. Supporting Evidence: PMID:18836529 smg-1 inactivation confers a resistance to oxidative stress in a daf-18-, daf-16- and cep-1-dependent manner |
| GO:0008270 zinc ion binding | IDA PMID:17581633 Structural evolution of C-terminal domains in the p53 family... | UNDECIDED | Summary: Zinc coordination is plausible for the CEP-1 p53-family DNA-binding domain but is not directly supported by the cached C-terminal-structure paper. Reason: UniProt maps zinc-binding residues in the CEP-1 DNA-binding domain, and the 2004 structure paper describes the DNA/Zn-binding loops of the p53 fold, but the IDA row cites the 2007 C-terminal oligomerization-domain paper and the local cache does not expose direct CEP-1 zinc-binding evidence. Leave this for structural recheck before accepting or removing. Supporting Evidence: PMID:15242600 three loops, involved in DNA and Zn binding in human p53, contain small alpha helices in Cep-1 |
| GO:0008270 zinc ion binding | ISS PMID:15242600 Structural differences in the DNA binding domains of human p... | UNDECIDED | Summary: Zinc coordination is plausible for the CEP-1 p53-family DNA-binding domain but is not directly supported by the cached C-terminal-structure paper. Reason: UniProt maps zinc-binding residues in the CEP-1 DNA-binding domain, and the 2004 structure paper describes the DNA/Zn-binding loops of the p53 fold, but the IDA row cites the 2007 C-terminal oligomerization-domain paper and the local cache does not expose direct CEP-1 zinc-binding evidence. Leave this for structural recheck before accepting or removing. Supporting Evidence: PMID:15242600 three loops, involved in DNA and Zn binding in human p53, contain small alpha helices in Cep-1 |
| GO:0008340 determination of adult lifespan | IMP PMID:11557844 Caenorhabditis elegans p53: role in apoptosis, meiosis, and ... | KEEP AS NON CORE | Summary: CEP-1 modulates adult lifespan in several genetic and stress contexts, but this is peripheral to its direct DNA-damage apoptosis role. Reason: Early cep-1 work reported decreased longevity under starvation stress, reduced cep-1 expression extends lifespan, and the SMG-1 longevity branch requires cep-1. These genetics support the broad lifespan term but not as a core molecular output of CEP-1. Supporting Evidence: PMID:11557844 decreased longevity in response to starvation-induced stress PMID:18836529 cep-1 RNAi partially suppressed the extension of lifespan due to smg-1 inhibition |
| GO:0008340 determination of adult lifespan | IMP PMID:17895432 Reduced expression of the Caenorhabditis elegans p53 ortholo... | KEEP AS NON CORE | Summary: CEP-1 modulates adult lifespan in several genetic and stress contexts, but this is peripheral to its direct DNA-damage apoptosis role. Reason: Early cep-1 work reported decreased longevity under starvation stress, reduced cep-1 expression extends lifespan, and the SMG-1 longevity branch requires cep-1. These genetics support the broad lifespan term but not as a core molecular output of CEP-1. Supporting Evidence: PMID:11557844 decreased longevity in response to starvation-induced stress PMID:18836529 cep-1 RNAi partially suppressed the extension of lifespan due to smg-1 inhibition |
| GO:0008340 determination of adult lifespan | IMP PMID:18836529 A novel role for the SMG-1 kinase in lifespan and oxidative ... | KEEP AS NON CORE | Summary: CEP-1 modulates adult lifespan in several genetic and stress contexts, but this is peripheral to its direct DNA-damage apoptosis role. Reason: Early cep-1 work reported decreased longevity under starvation stress, reduced cep-1 expression extends lifespan, and the SMG-1 longevity branch requires cep-1. These genetics support the broad lifespan term but not as a core molecular output of CEP-1. Supporting Evidence: PMID:11557844 decreased longevity in response to starvation-induced stress PMID:18836529 cep-1 RNAi partially suppressed the extension of lifespan due to smg-1 inhibition |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IMP PMID:19521535 Caenorhabditis elegans protein arginine methyltransferase PR... | MODIFY | Summary: The PRMT-5/CBP-1 evidence concerns CEP-1-dependent DNA-damage apoptosis and can be represented with the p53-class mediator child term. Reason: Loss of prmt-5 increases ionizing-radiation-induced germ-cell apoptosis through CEP-1-dependent egl-1 transcription. Because CEP-1 is the p53-family transcriptional effector in this pathway, the p53-specific DNA-damage intrinsic apoptosis term is more precise than its parent. Proposed replacements: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Supporting Evidence: PMID:19521535 PRMT-5 forms a complex with both CEP-1 and CBP-1 and can methylate the latter PMID:19521535 PRMT-5 likely represses CEP-1 transcriptional activity through CBP-1 |
| GO:0017053 transcription repressor complex | IPI PMID:19521535 Caenorhabditis elegans protein arginine methyltransferase PR... | KEEP AS NON CORE | Summary: CEP-1 forms a PRMT-5/CBP-1 complex that represses the DNA-damage apoptotic transcriptional response. Reason: Coimmunoprecipitation and functional data support a complex containing PRMT-5, CEP-1 and CBP-1. This is an upstream restraint on CEP-1 activity rather than the central DNA-binding activator activity itself. Supporting Evidence: PMID:19521535 PRMT-5 forms a complex with both CEP-1 and CBP-1 and can methylate the latter PMID:19521535 PRMT-5 likely represses CEP-1 transcriptional activity through CBP-1 |
| GO:0042594 response to starvation | IMP PMID:11557844 Caenorhabditis elegans p53: role in apoptosis, meiosis, and ... | KEEP AS NON CORE | Summary: CEP-1 participates in starvation stress survival, a non-core somatic stress branch. Reason: The cached abstract reports reduced longevity in cep-1 mutants under starvation-induced stress. The full text is unavailable, so the proximal starvation-responsive target is not clear, but the broad stress-response row can be retained as non-core. Supporting Evidence: PMID:11557844 decreased longevity in response to starvation-induced stress |
| GO:0042770 signal transduction in response to DNA damage | IDA PMID:18340346 The SCF FSN-1 ubiquitin ligase controls germline apoptosis t... | MODIFY | Summary: The FSN-1 evidence is specifically about regulation of CEP-1-dependent DNA-damage germline apoptosis. Reason: The broad DNA-damage signal-transduction row can be narrowed to the CEP-1/p53-mediated intrinsic apoptotic branch because FSN-1 loss elevates endogenous CEP-1 activity and is suppressed by a cep-1 loss-of-function allele in ENU-induced germline apoptosis. Proposed replacements: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Supporting Evidence: PMID:18340346 cep-1-dependent germline apoptosis PMID:18340346 transcriptional activity, phosphorylation status, and levels of endogenous CEP-1 are higher in |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IDA PMID:17186023 Regulation of developmental rate and germ cell proliferation... | ACCEPT | Summary: CEP-1 mediates germline intrinsic apoptosis after DNA damage by activating BH3-only transcriptional targets. Reason: Multiple independent DNA-damage studies show that ionizing radiation, UV-C, or checkpoint activation route through CEP-1 to induce egl-1 and ced-13 and thereby trigger the core CED-9/CED-4/CED-3 apoptotic module. Supporting Evidence: PMID:17186023 Caenorhabditis elegans CEP-1 activates germline apoptosis in response to genotoxic stress |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IDA PMID:18627611 Transcriptional profiling in C. elegans suggests DNA damage ... | ACCEPT | Summary: CEP-1 mediates germline intrinsic apoptosis after DNA damage by activating BH3-only transcriptional targets. Reason: Multiple independent DNA-damage studies show that ionizing radiation, UV-C, or checkpoint activation route through CEP-1 to induce egl-1 and ced-13 and thereby trigger the core CED-9/CED-4/CED-3 apoptotic module. Supporting Evidence: PMID:18627611 Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene PMID:18627611 DNA damage induced apoptosis via the transcriptional induction of BH3 domain proteins is likely to be an ancient DNA damage response function of the p53 family |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IGI PMID:12684824 Genetic and cytological characterization of the recombinatio... | UNDECIDED | Summary: The RAD-51 IGI apoptosis row cannot be checked from the abstract-only cache. Reason: The cached PMID:12684824 record is abstract-only and foregrounds rad-51 meiotic recombination rather than exposing the cep-1 genetic-interaction experiment behind the WormBase IGI row. Keep the experimental row unresolved pending a full-text or WormBase evidence recheck. |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IMP PMID:11557844 Caenorhabditis elegans p53: role in apoptosis, meiosis, and ... | ACCEPT | Summary: CEP-1 mediates germline intrinsic apoptosis after DNA damage by activating BH3-only transcriptional targets. Reason: Multiple independent DNA-damage studies show that ionizing radiation, UV-C, or checkpoint activation route through CEP-1 to induce egl-1 and ced-13 and thereby trigger the core CED-9/CED-4/CED-3 apoptotic module. Supporting Evidence: PMID:11696333 damage-induced apoptosis in the C. elegans germline PMID:12445383 DNA damage increases expression of the proapoptotic gene egl-1, a response that requires hus-1 and the p53 homolog cep-1 PMID:15605074 ced-13 mRNA accumulates following DNA damage, and that this accumulation is dependent on an intact C. elegans cep-1/p53 gene |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IMP PMID:11696333 The C. elegans homolog of the p53 tumor suppressor is requir... | ACCEPT | Summary: CEP-1 mediates germline intrinsic apoptosis after DNA damage by activating BH3-only transcriptional targets. Reason: Multiple independent DNA-damage studies show that ionizing radiation, UV-C, or checkpoint activation route through CEP-1 to induce egl-1 and ced-13 and thereby trigger the core CED-9/CED-4/CED-3 apoptotic module. Supporting Evidence: PMID:11696333 damage-induced apoptosis in the C. elegans germline PMID:12445383 DNA damage increases expression of the proapoptotic gene egl-1, a response that requires hus-1 and the p53 homolog cep-1 PMID:15605074 ced-13 mRNA accumulates following DNA damage, and that this accumulation is dependent on an intact C. elegans cep-1/p53 gene |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IMP PMID:12445383 Caenorhabditis elegans HUS-1 is a DNA damage checkpoint prot... | ACCEPT | Summary: CEP-1 mediates germline intrinsic apoptosis after DNA damage by activating BH3-only transcriptional targets. Reason: Multiple independent DNA-damage studies show that ionizing radiation, UV-C, or checkpoint activation route through CEP-1 to induce egl-1 and ced-13 and thereby trigger the core CED-9/CED-4/CED-3 apoptotic module. Supporting Evidence: PMID:12445383 DNA damage increases expression of the proapoptotic gene egl-1, a response that requires hus-1 and the p53 homolog cep-1 PMID:15605074 ced-13 mRNA accumulates following DNA damage, and that this accumulation is dependent on an intact C. elegans cep-1/p53 gene |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IMP PMID:15605074 C. elegans ced-13 can promote apoptosis and is induced in re... | ACCEPT | Summary: CEP-1 mediates germline intrinsic apoptosis after DNA damage by activating BH3-only transcriptional targets. Reason: Multiple independent DNA-damage studies show that ionizing radiation, UV-C, or checkpoint activation route through CEP-1 to induce egl-1 and ced-13 and thereby trigger the core CED-9/CED-4/CED-3 apoptotic module. Supporting Evidence: PMID:15605074 ced-13 mRNA accumulates following DNA damage, and that this accumulation is dependent on an intact C. elegans cep-1/p53 gene PMID:15605074 p53 promotes cell death by inducing expression of two BH3-only genes |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IMP PMID:17347667 The nucleotide excision repair pathway is required for UV-C-... | ACCEPT | Summary: CEP-1 mediates germline intrinsic apoptosis after DNA damage by activating BH3-only transcriptional targets. Reason: Multiple independent DNA-damage studies show that ionizing radiation, UV-C, or checkpoint activation route through CEP-1 to induce egl-1 and ced-13 and thereby trigger the core CED-9/CED-4/CED-3 apoptotic module. Supporting Evidence: PMID:17347667 Both UV-induced apoptosis and cell cycle arrest were completely dependent on the p53 homolog CEP-1 |
| GO:0042803 protein homodimerization activity | IDA PMID:17581633 Structural evolution of C-terminal domains in the p53 family... | ACCEPT | Summary: The CEP-1 C-terminal oligomerization/SAM region forms a homodimeric p53-family oligomerization domain. Reason: NMR and hydrodynamic analysis showed that the C-terminal oligomerization domain of CEP-1 is dimeric rather than tetrameric like vertebrate p53. Supporting Evidence: PMID:17581633 CEP-1 contains a composite domain of an OD and a sterile alpha motif (SAM) domain, and forms dimers instead of tetramers |
| GO:0043565 sequence-specific DNA binding | IDA PMID:15242600 Structural differences in the DNA binding domains of human p... | MODIFY | Summary: Sequence-specific DNA binding is true but should be represented by the transcription activator molecular function. Reason: The crystallized CEP-1 DNA-binding domain is part of a p53-family transcription activator that binds response elements and activates target-gene transcription; the MF can therefore be raised to DNA-binding transcription activator activity. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:15242600 recognize essentially identical DNA sequences despite poor sequence similarity PMID:11696333 transcription factor and is able to activate a transcriptional reporter PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo |
| GO:0045132 meiotic chromosome segregation | IMP PMID:11557844 Caenorhabditis elegans p53: role in apoptosis, meiosis, and ... | KEEP AS NON CORE | Summary: CEP-1 affects meiotic chromosome segregation in the germ line, but this developmental genome-quality role is non-core here. Reason: The original cep-1 paper reports that the gene is required for normal meiotic chromosome segregation. The full text is unavailable, so retain this as a non-core curated WormBase/UniProt phenotype rather than using it to define CEP-1 core function. Supporting Evidence: PMID:11557844 required for normal meiotic chromosome segregation in the germ line |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16582625 The fatty acid synthase gene is a conserved p53 family targe... | ACCEPT | Summary: CEP-1 directly activates RNA polymerase II target-gene transcription. Reason: The fasn-1 study showed that CEP-1 binds p53-family response elements in the fasn-1 gene and modulates fasn-1 expression in vivo, directly supporting positive regulation of Pol II transcription. Supporting Evidence: PMID:16582625 CEP-1, the C. elegans p53 homolog, is able to bind the two p53 family responsive elements (REs) identified in the worm fasn-1 gene PMID:16582625 fasn-1 expression is modulated by CEP-1 in vivo |
| GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator | IGI PMID:25340700 It's all in your mind: determining germ cell fate by neurona... | KEEP AS NON CORE | Summary: Neuronal IRE-1 activation uses CEP-1 to induce germ-cell intrinsic apoptosis independently of DNA damage. Reason: ER stress sensed through neuronal IRE-1 raises CEP-1 in germ cells and triggers the same downstream apoptosis machinery, but this systemic non-DNA-damage input is a specialized stress branch rather than the canonical CEP-1 DNA-damage response. Supporting Evidence: PMID:25340700 increases CEP-1 levels in the germ cells, which triggers germ cell apoptosis PMID:25340700 activate CEP-1 independently of DNA damage upon activation of neuronal IRE-1 |
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Download this section (compressed HTML)Q: Which CEP-1 targets mediate the hypoxia, starvation, oxidative-stress, and lifespan phenotypes, and are they direct transcriptional targets rather than indirect organismal stress readouts?
Suggested experts: Rothman JH, Derry WB, Solari F
Q: Is the PRMT-5/CBP-1/CEP-1 complex a stable endogenous transcription repressor complex at egl-1 and ced-13 promoters, or a transient regulatory assembly on CEP-1?
Suggested experts: Yang C
Experiment: Perform CEP-1 ChIP-seq or CUT&RUN together with matched RNA-seq after ionizing radiation, UV-C, oxidative stress, hypoxia, starvation, and neuronal IRE-1 activation, and compare wild-type, cep-1-null, and PRMT-5/CBP-1-perturbed germ lines.
Hypothesis: A compact, stress-specific subset of CEP-1 genomic binding events drives DNA-damage apoptosis while other CEP-1 targets drive non-apoptotic stress and lifespan outputs.
Type: comparative ChIP-seq/RNA-seq stress-response profiling
Experiment: Rescue cep-1 mutants with separation-of-function DNA-binding-domain, dimerization-interface, and SAM-domain alleles, then measure egl-1 and ced-13 induction, germ-cell corpses, and fasn-1 or phg-1 target expression after DNA damage.
Hypothesis: The CEP-1 oligomerization/SAM domain is required for apoptotic target-gene activation independently of DNA binding.
Type: structure-function rescue assay
cep-1 encodes an ortholog of the human tumor suppressor p53 (OMIM:191170, mutated in Li-Fraumeni syndrome) that promotes DNA damage-induced apoptosis and is required for normal meiotic segregation in the germ line, and affects sensitivity to hypoxia-induced lethality and longevity in response to starvation; CEP-1 is expressed ubiquitously in embryos and in the nucleoli of a subset of pharyngeal cells.
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