Affiliation:
1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch cedex, France
Abstract
ABSTRACT
The tumor suppressor function of p53 is linked to its ability to repress gene expression, but the mechanisms of specific gene repression are poorly understood. We report that wild-type p53 inhibits an effector of the Ras oncogene/mitogen-activated protein (MAP) kinase pathway, the transcription factor Net. Tumor-associated mutant p53s are less efficient inhibitors. p53 inhibits by preventing phosphorylation of Net by MAP kinases. Loss of p53 in vivo leads to increased Net phosphorylation in response to wound healing and UV irradiation of skin. Our results show that p53 can repress specific gene expression by inhibiting Net, a factor implicated in cell cycle entry.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference52 articles.
1. Agoff, S. N., J. Hou, D. I. Linzer, and B. Wu. 1993. Regulation of the human hsp70 promoter by p53. Science259:84-87.
2. Ayadi, A., H. Zheng, P. Sobieszczuk, G. Buchwalter, P. Moerman, K. Alitalo, and B. Wasylyk. 2001. Net-targeted mutant mice develop a vascular phenotype and up-regulate egr-1. EMBO J.20:5139-5152.
3. Bargonetti, J., A. Chicas, D. White, and C. Prives. 1997. p53 represses Sp1 DNA binding and HIV-LTR directed transcription. Cell. Mol. Biol. (Noisy-le-grand)43:935-949.
4. Bergers, G., K. Javaherian, K. M. Lo, J. Folkman, and D. Hanahan. 1999. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science284:808-812.
5. Brou, C., S. Chaudhary, I. Davidson, Y. Lutz, J. Wu, J. M. Egly, L. Tora, and P. Chambon. 1993. Distinct TFIID complexes mediate the effect of different transcriptional activators. EMBO J.12:489-499.
Cited by
16 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献