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The SCF FSN-1 ubiquitin ligase controls germline apoptosis through CEP-1/p53 in C. elegans.
Cell Death Differ. 2008 Jun; 15(6):1054-62.CD

Abstract

The nematode Caenorhabditis elegans contains a single ancestral p53 family member, cep-1, which is required to activate apoptosis of germ cells in response to DNA damage. To understand how the cep-1/p53 pathway is regulated in response to genotoxic stress, we performed an RNA interference screen and identified the neddylation pathway and components of an SCF (Skp1/cullin/F-box) E3 ubiquitin ligase as negative regulators of cep-1-dependent germ cell apoptosis. Here, we show that the cullin gene cul-1, the Skp1-related gene skr-1, and the ring box genes rbx-1 and rpm-1 all negatively regulate cep-1-dependent germ cell apoptosis in response to the DNA-alkylating agent N-ethyl-N-nitrosourea (ENU). We also identified the F-box protein FSN-1, previously shown to form an SCF ligase that regulates synapse development, as a negative regulator of cep-1-dependent germline apoptosis. The hypersensitivity of fsn-1 mutants to ENU-induced germline apoptosis was completely suppressed by a cep-1 loss-of-function allele. We further provide evidence that the transcriptional activity, phosphorylation status, and levels of endogenous CEP-1 are higher in fsn-1 mutants compared with wild-type animals after ENU treatment. Our results uncover a novel role for the SCF(FSN-1) E3 ubiquitin ligase in the regulation of cep-1-dependent germ cell apoptosis.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Gao MX
Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto Medical Discovery Tower, 101 College Street, Toronto, Ontario, Canada.
Liao EH
No affiliation info available
Yu B
No affiliation info available
Wang Y
No affiliation info available
Zhen M
No affiliation info available
Derry WB
No affiliation info available

MeSH

AnimalsApoptosisCaenorhabditis elegansCaenorhabditis elegans ProteinsDNA DamageF-Box ProteinsGerm CellsMutationNEDD8 ProteinRNA InterferenceSKP Cullin F-Box Protein LigasesSignal TransductionTranscription, GeneticTumor Suppressor Protein p53Ubiquitins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18340346

Citation

Gao, M X., et al. "The SCF FSN-1 Ubiquitin Ligase Controls Germline Apoptosis Through CEP-1/p53 in C. Elegans." Cell Death and Differentiation, vol. 15, no. 6, 2008, pp. 1054-62.
Gao MX, Liao EH, Yu B, et al. The SCF FSN-1 ubiquitin ligase controls germline apoptosis through CEP-1/p53 in C. elegans. Cell Death Differ. 2008;15(6):1054-62.
Gao, M. X., Liao, E. H., Yu, B., Wang, Y., Zhen, M., & Derry, W. B. (2008). The SCF FSN-1 ubiquitin ligase controls germline apoptosis through CEP-1/p53 in C. elegans. Cell Death and Differentiation, 15(6), 1054-62. https://doi.org/10.1038/cdd.2008.30
Gao MX, et al. The SCF FSN-1 Ubiquitin Ligase Controls Germline Apoptosis Through CEP-1/p53 in C. Elegans. Cell Death Differ. 2008;15(6):1054-62. PubMed PMID: 18340346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The SCF FSN-1 ubiquitin ligase controls germline apoptosis through CEP-1/p53 in C. elegans. AU - Gao,M X, AU - Liao,E H, AU - Yu,B, AU - Wang,Y, AU - Zhen,M, AU - Derry,W B, Y1 - 2008/03/14/ PY - 2008/3/15/pubmed PY - 2008/7/29/medline PY - 2008/3/15/entrez SP - 1054 EP - 62 JF - Cell death and differentiation JO - Cell Death Differ VL - 15 IS - 6 N2 - The nematode Caenorhabditis elegans contains a single ancestral p53 family member, cep-1, which is required to activate apoptosis of germ cells in response to DNA damage. To understand how the cep-1/p53 pathway is regulated in response to genotoxic stress, we performed an RNA interference screen and identified the neddylation pathway and components of an SCF (Skp1/cullin/F-box) E3 ubiquitin ligase as negative regulators of cep-1-dependent germ cell apoptosis. Here, we show that the cullin gene cul-1, the Skp1-related gene skr-1, and the ring box genes rbx-1 and rpm-1 all negatively regulate cep-1-dependent germ cell apoptosis in response to the DNA-alkylating agent N-ethyl-N-nitrosourea (ENU). We also identified the F-box protein FSN-1, previously shown to form an SCF ligase that regulates synapse development, as a negative regulator of cep-1-dependent germline apoptosis. The hypersensitivity of fsn-1 mutants to ENU-induced germline apoptosis was completely suppressed by a cep-1 loss-of-function allele. We further provide evidence that the transcriptional activity, phosphorylation status, and levels of endogenous CEP-1 are higher in fsn-1 mutants compared with wild-type animals after ENU treatment. Our results uncover a novel role for the SCF(FSN-1) E3 ubiquitin ligase in the regulation of cep-1-dependent germ cell apoptosis. SN - 1350-9047 UR - https://www.unboundmedicine.com/medline/citation/18340346/The_SCF_FSN_1_ubiquitin_ligase_controls_germline_apoptosis_through_CEP_1/p53_in_C__elegans_ DB - PRIME DP - Unbound Medicine ER -