cep-1

UniProt ID: A8WW61
Organism: Caenorhabditis briggsae
Review Status: INITIALIZED
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Gene Description

Cbr-CEP-1 is the Caenorhabditis briggsae ortholog of the nematode p53/p63/p73-family transcription factor CEP-1, the sole representative of the p53 superfamily in Caenorhabditis. It is a sequence-specific, zinc-dependent DNA-binding transcription factor that recognizes a p53-like DNA consensus element and acts predominantly as a transcriptional activator. Its central, conserved role is to trigger germline apoptosis in response to genotoxic stress (ionizing radiation and other DNA-damaging insults), acting downstream of DNA-damage signaling by directly inducing transcription of the BH3-only pro-apoptotic activators egl-1 and ced-13. It also contributes to physiological roles outside DNA-damage apoptosis, including ensuring proper meiotic chromosome segregation, modulating responses to additional stresses such as hypoxia, oxidative stress and starvation, regulating germline proliferation (via phg-1), and negatively influencing adult lifespan. The protein binds one zinc ion per subunit through its p53-like DNA-binding domain, functions as a homodimer, and its pro-apoptotic activity is modulated by interacting partners (for example inhibition by ape-1 and by methylated cbp-1 in the prmt-5/cbp-1 complex). Like vertebrate p53, it functions in the nucleus.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003677 DNA binding
IEA
GO_REF:0000120
MARK AS OVER ANNOTATED
Summary: CEP-1 is a bona fide DNA-binding protein, so this is not wrong, but DNA binding is a generic parent term. The more specific and informative molecular functions (sequence-specific DNA binding and DNA-binding transcription factor activity) are separately annotated and better capture the function.
GO:0003700 DNA-binding transcription factor activity
IEA
GO_REF:0000120
MODIFY
Summary: CEP-1 is the worm p53-family transcription factor and binds a p53-like DNA consensus to activate transcription of target genes. This is a core molecular function. I propose a more specific RNA polymerase II-specific term as the core function, but the general term is correct.
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: As a transcription factor, CEP-1 acts in the nucleus; UniProt records nuclear localization by similarity to the C. elegans ortholog. Core cellular component for a transcription factor.
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: CEP-1 regulates transcription of target genes. This is correct but very general; the RNA polymerase II-specific positive-regulation term better reflects its activator role. Retained as a non-core, broader process annotation.
GO:0001666 response to hypoxia
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: CEP-1 promotes apoptosis under hypoxic and other stress conditions (UniProt FUNCTION). This is a peripheral stress-response process for a pleiotropic transcription factor, kept as non-core.
GO:0005654 nucleoplasm
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Consistent with nuclear localization of a transcription factor. Reasonable but more granular than needed; subsumed by the nucleus annotation, kept as non-core.
GO:0005730 nucleolus
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: Nucleolar localization is not part of the established function of worm p53/CEP-1, which acts as a sequence-specific transcription factor in the nucleoplasm. This electronically propagated component looks like an over-reach not supported by CEP-1 biology.
GO:0006979 response to oxidative stress
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: CEP-1 promotes apoptosis under conditions of cellular and genotoxic stress, consistent with a role in oxidative-stress responses. Peripheral process for this pleiotropic TF, kept as non-core.
GO:0008270 zinc ion binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: The p53-like DNA-binding domain coordinates one zinc ion per subunit (UniProt COFACTOR and BINDING sites at residues 319, 322, 375, 379). Correct and structurally supported, though it is an accessory binding function supporting DNA binding rather than the core function.
GO:0008340 determination of adult lifespan
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: CEP-1 negatively regulates lifespan (UniProt FUNCTION). A genuine but peripheral organismal-level role for this pleiotropic transcription factor, kept as non-core.
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
IEA
GO_REF:0000107
ACCEPT
Summary: CEP-1 is the central mediator of DNA-damage-induced germline apoptosis, acting downstream of DNA-damage signaling to induce egl-1 and ced-13. This is a core biological process. The p53-class-mediator child term is the most specific representation.
GO:0017053 transcription repressor complex
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: CEP-1 functions predominantly as a transcriptional activator of pro-apoptotic targets. While it interacts with the prmt-5/cbp-1 complex (which can inhibit its activity), placement in a transcription repressor complex mischaracterizes its primary role and is an over-reach of an electronically propagated component annotation.
GO:0042594 response to starvation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: CEP-1 promotes apoptosis under starvation among other stress conditions (UniProt FUNCTION). Peripheral stress-response process for this pleiotropic TF, kept as non-core.
GO:0042770 signal transduction in response to DNA damage
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: CEP-1 acts in the DNA-damage response and is itself induced and phosphorylated following DNA damage. It functions as the transcriptional effector at the end of the pathway; the DNA-damage apoptotic-signaling terms capture this best. Kept as a non-core supporting process.
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
IEA
GO_REF:0000107
ACCEPT
Summary: This is the single most specific and accurate process term for CEP-1, the worm p53-class mediator of DNA-damage-induced germline apoptosis (inducing egl-1/ced-13). Core biological process.
GO:0042803 protein homodimerization activity
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: CEP-1 functions as a homodimer (UniProt SUBUNIT), consistent with p53-family DNA binding. Correct accessory molecular function supporting DNA binding; kept as non-core.
GO:0043565 sequence-specific DNA binding
IEA
GO_REF:0000107
ACCEPT
Summary: CEP-1 binds the same DNA consensus sequence as p53 (UniProt FUNCTION) via its p53-like DNA-binding domain. This is a core molecular function underpinning its activity as a sequence-specific transcription factor.
GO:0045132 meiotic chromosome segregation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: CEP-1 has a normal developmental role ensuring proper meiotic chromosome segregation (UniProt FUNCTION). A genuine but non-core developmental process distinct from its DNA-damage apoptotic role.
GO:0045944 positive regulation of transcription by RNA polymerase II
IEA
GO_REF:0000107
ACCEPT
Summary: CEP-1 is primarily a transcriptional activator, directly inducing target genes (egl-1, ced-13, phg-1) via RNA polymerase II. This accurately captures its mode of action as an activator and is treated as core together with the DNA-damage apoptosis role.
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Correct parent term describing CEP-1 as a p53-class mediator of intrinsic apoptosis. The DNA-damage-specific child (GO:0042771) is more precise and treated as core; this broader term is retained as non-core.
GO:0005634 nucleus
ISS
GO_REF:0000024
ACCEPT
Summary: Duplicate of the nucleus localization (here by ISS from the C. elegans ortholog). CEP-1 acts in the nucleus; core component for a transcription factor.
GO:0001666 response to hypoxia
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: ISS duplicate of the hypoxia-response annotation. CEP-1 promotes apoptosis under hypoxic stress; peripheral process, kept as non-core.
GO:0003700 DNA-binding transcription factor activity
ISS
GO_REF:0000024
MODIFY
Summary: ISS transfer of the core transcription factor activity from the C. elegans ortholog. Correct; the RNA polymerase II-specific term is proposed as the most precise core molecular function.
GO:0006355 regulation of DNA-templated transcription
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: ISS duplicate. Correct but very general regulation-of-transcription term; retained as non-core in favor of the RNA polymerase II-specific positive regulation term.
GO:0006979 response to oxidative stress
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: ISS duplicate of the oxidative-stress response. Peripheral stress process for this pleiotropic TF, kept as non-core.
GO:0008270 zinc ion binding
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: ISS duplicate. The DNA-binding domain coordinates one zinc ion per subunit; accessory binding function supporting DNA binding, kept as non-core.
GO:0008340 determination of adult lifespan
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: ISS duplicate. CEP-1 negatively regulates lifespan; peripheral organismal role, kept as non-core.
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
ISS
GO_REF:0000024
ACCEPT
Summary: ISS transfer of the most specific and accurate process term: CEP-1 as the worm p53-class mediator of DNA-damage-induced germline apoptosis. Core biological process.
GO:0042803 protein homodimerization activity
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: ISS duplicate. CEP-1 acts as a homodimer; accessory molecular function supporting DNA binding, kept as non-core.
GO:0043565 sequence-specific DNA binding
ISS
GO_REF:0000024
ACCEPT
Summary: ISS transfer of sequence-specific DNA binding, a core molecular function. CEP-1 binds a p53-like consensus via its DNA-binding domain.
GO:0045132 meiotic chromosome segregation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: ISS duplicate. Genuine developmental role ensuring proper meiotic chromosome segregation, distinct from the core DNA-damage apoptosis function; kept as non-core.

Core Functions

Sequence-specific RNA polymerase II DNA-binding transcription factor that binds a p53-like DNA consensus element and activates transcription of target genes.

Supporting Evidence:
  • GO_REF:0000024
    Transcriptional activator that binds the same DNA consensus sequence as p53.

As the worm p53-class mediator, drives the intrinsic apoptotic response to DNA damage by transactivating pro-apoptotic BH3-only target genes (egl-1, ced-13) to trigger germline apoptosis after genotoxic stress.

Supporting Evidence:
  • GO_REF:0000024
    Regulates DNA damage-induced apoptosis by inducing transcription of the programmed cell death activator egl-1.

References

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