The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis

Citation
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
Citations number
28
Categorie Soggetti
Experimental Biology
Journal title
CURRENT BIOLOGY
ISSN journal
09609822 → ACNP
Volume
11
Issue
21
Year of publication
2001
Pages
1722 - 1727
Database
ISI
SICI code
0960-9822(20011030)11:21<1722:TCEHOT>2.0.ZU;2-6
Abstract
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.