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Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis.
Cell. 2005 Feb 11; 120(3):357-68.Cell

Abstract

p53 is a tumor suppressor gene whose regulation is crucial to maintaining genome stability and for the apoptotic elimination of abnormal, potentially cancer-predisposing cells. C. elegans contains a primordial p53 gene, cep-1, that acts as a transcription factor necessary for DNA damage-induced apoptosis. In a genetic screen for negative regulators of CEP-1, we identified a mutation in GLD-1, a translational repressor implicated in multiple C. elegans germ cell fate decisions and related to mammalian Quaking proteins. CEP-1-dependent transcription of proapoptotic genes is upregulated in the gld-1(op236) mutant and an elevation of p53-mediated germ cell apoptosis in response to DNA damage is observed. Further, we demonstrate that GLD-1 mediates its repressive effect by directly binding to the 3'UTR of cep-1/p53 mRNA and repressing its translation. This study reveals that the regulation of cep-1/p53 translation influences DNA damage-induced apoptosis and demonstrates the physiological importance of this mechanism.

Authors+Show Affiliations

Department of Cell Biology, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18a, D 82152 Martinsried, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15707894

Citation

Schumacher, Björn, et al. "Translational Repression of C. Elegans P53 By GLD-1 Regulates DNA Damage-induced Apoptosis." Cell, vol. 120, no. 3, 2005, pp. 357-68.
Schumacher B, Hanazawa M, Lee MH, et al. Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. Cell. 2005;120(3):357-68.
Schumacher, B., Hanazawa, M., Lee, M. H., Nayak, S., Volkmann, K., Hofmann, E. R., Hofmann, R., Hengartner, M., Schedl, T., & Gartner, A. (2005). Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. Cell, 120(3), 357-68.
Schumacher B, et al. Translational Repression of C. Elegans P53 By GLD-1 Regulates DNA Damage-induced Apoptosis. Cell. 2005 Feb 11;120(3):357-68. PubMed PMID: 15707894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis. AU - Schumacher,Björn, AU - Hanazawa,Momoyo, AU - Lee,Min-Ho, AU - Nayak,Sudhir, AU - Volkmann,Katrin, AU - Hofmann,E Randal, AU - Hofmann,Randall, AU - Hengartner,Michael, AU - Schedl,Tim, AU - Gartner,Anton, PY - 2004/07/04/received PY - 2004/10/27/revised PY - 2004/12/08/accepted PY - 2005/2/15/pubmed PY - 2005/3/30/medline PY - 2005/2/15/entrez SP - 357 EP - 68 JF - Cell JO - Cell VL - 120 IS - 3 N2 - p53 is a tumor suppressor gene whose regulation is crucial to maintaining genome stability and for the apoptotic elimination of abnormal, potentially cancer-predisposing cells. C. elegans contains a primordial p53 gene, cep-1, that acts as a transcription factor necessary for DNA damage-induced apoptosis. In a genetic screen for negative regulators of CEP-1, we identified a mutation in GLD-1, a translational repressor implicated in multiple C. elegans germ cell fate decisions and related to mammalian Quaking proteins. CEP-1-dependent transcription of proapoptotic genes is upregulated in the gld-1(op236) mutant and an elevation of p53-mediated germ cell apoptosis in response to DNA damage is observed. Further, we demonstrate that GLD-1 mediates its repressive effect by directly binding to the 3'UTR of cep-1/p53 mRNA and repressing its translation. This study reveals that the regulation of cep-1/p53 translation influences DNA damage-induced apoptosis and demonstrates the physiological importance of this mechanism. SN - 0092-8674 UR - https://www.unboundmedicine.com/medline/citation/15707894/Translational_repression_of_C__elegans_p53_by_GLD_1_regulates_DNA_damage_induced_apoptosis_ DB - PRIME DP - Unbound Medicine ER -