The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis.
In mammals, one of the key regulators necessary for responding to genotoxic stress is the p53 transcription factor. p53 is the single most commonly mutated tumor suppressor gene in human cancers. Here we report the identification of a C. elegans homolog of mammalian p53. Using RNAi and DNA cosuppression technology, we show that C. elegans p53 (cep-1) is required for DNA damage-induced apoptosis in the C. elegans germline. However,cep-1 RNAi does not affect programmed cell death occurring during worm development and physiological (radiation-independent) germ cell death. The DNA binding domain of CEP-1 is related to vertebrate p53 members and possesses the conserved residues most frequently mutated in human tumors. Consistent with this, CEP-1 acts as a transcription factor and is able to activate a transcriptional reporter containing consensus human p53 binding sites. Our data support the notion that p53-mediated transcriptional regulation is part of an ancestral pathway mediating DNA damage-induced apoptosis and reveals C. elegans as a genetically tractable model organism for studying the p53 apoptotic pathway.
Schumacher
B
B
Max Planck Institut für Biochemie, Department of Cell Biology, Am Klopferspitz 18A, 82152 Martinsried, Germany.
Hofmann
K
K
Boulton
S
S
Gartner
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D004249:DNA Damage; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C438244:CEP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53