B. Schumacher et al., The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis, CURR BIOL, 11(21), 2001, pp. 1722-1727
In mammals, one of the key regulators necessary for responding to genotoxic
stress is the p53 transcription factor. p53 is the single most commonly mu
tated tumor suppressor gene in human cancers [1]. Here we report the identi
fication of a C. elegans homolog of mammalian p53. Using RNAi and DNA cosup
pression technology, we show that C. elegans p53 (cep-1) is required for DN
A 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 dom
ain of CEP-1 is related to vertebrate p53 members and possesses the conserv
ed residues most frequently mutated in human tumors. Consistent with this,
CEP-1 acts as a transcription factor and is able to activate a transcriptio
nal reporter containing consensus human p53 binding sites. Our data support
the notion that p53-mediated transcriptional regulation is part of an ance
stral pathway mediating DNA damage-induced apoptosis and reveals C. elegans
as a genetically tractable model organism for studying the p53 apoptotic p
athway.