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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

Schumacher B
Department of Cell Biology, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18a, D 82152 Martinsried, Germany.
Hanazawa M
No affiliation info available
Lee MH
No affiliation info available
Nayak S
No affiliation info available
Volkmann K
No affiliation info available
Hofmann ER
No affiliation info available
Hofmann R
No affiliation info available
Hengartner M
No affiliation info available
Schedl T
No affiliation info available
Gartner A
No affiliation info available

MeSH

3' Untranslated RegionsAnimalsApoptosisBinding SitesCaenorhabditis elegansCaenorhabditis elegans ProteinsDNA DamageFemaleGene Expression RegulationGerm CellsMaleMutationRNA, MessengerRepressor ProteinsSex DifferentiationTumor Suppressor Protein p53Up-Regulation

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 -