Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis

Cell. 2005 Feb 11;120(3):357-68. doi: 10.1016/j.cell.2004.12.009.


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.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / genetics*
  • Binding Sites / physiology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / biosynthesis*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA Damage / genetics
  • Female
  • Gene Expression Regulation / physiology*
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • Male
  • Mutation / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sex Differentiation / physiology
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Tumor Suppressor Protein p53 / genetics
  • Up-Regulation / genetics


  • 3' Untranslated Regions
  • CEP-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • GLD-1 protein, C elegans
  • RNA, Messenger
  • Repressor Proteins
  • Tumor Suppressor Protein p53