TY - JOUR
T1 - Translational repression of C. elegans p53 by GLD-1 regulates DNA damage-induced apoptosis
AU - Schumacher, Bjorn
AU - Hanazawa, Momoyo
AU - Lee, Min-Ho
AU - Nayak, Sudhir
AU - Volkmann, Katrin
AU - Hofmann, Randall
AU - Hengartner, Michael
AU - Schedl, Tim
AU - Gartner, Anton
N1 -
dc.publisher: Elsevier
PY - 2005/2
Y1 - 2005/2
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.
AB - 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.
U2 - 10.1016/j.cell.2004.12.009
DO - 10.1016/j.cell.2004.12.009
M3 - Article
SN - 0092-8674
VL - 120
SP - 357
EP - 368
JO - Cell
JF - Cell
IS - 3
ER -
