作者
Robin E Bachelder, Mark J Ribick, Alessandra Marchetti, Rita Falcioni, Silvia Soddu, Kathryn R Davis, Arthur M Mercurio
发表日期
1999/11/29
期刊
The Journal of cell biology
卷号
147
期号
5
页码范围
1063-1072
出版商
The Rockefeller University Press
简介
Although the interaction of matrix proteins with integrins is known to initiate signaling pathways that are essential for cell survival, a role for tumor suppressors in the regulation of these pathways has not been established. We demonstrate here that p53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase AKT/PKB. Specifically, we show that the α6β4 integrin promotes the survival of p53-deficient carcinoma cells by activating AKT/PKB. In contrast, this integrin does not activate AKT/PKB in carcinoma cells that express wild-type p53 and it actually stimulates their apoptosis, in agreement with our previous findings (Bachelder, R.E., A. Marchetti, R. Falcioni, S. Soddu, and A.M. Mercurio. 1999. J. Biol. Chem. 274:20733–20737). Interestingly, we observed reduced levels of AKT/PKB protein after antibody clustering of α6β4 in carcinoma …
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RE Bachelder, MJ Ribick, A Marchetti, R Falcioni… - The Journal of cell biology, 1999