APOPTOSIS Presence of p53 May Count in Cell Survival

Abstract: Adhesion of cells to the extracellular matrix regulates cell survival through the activation of cell surface integrins and their associated signaling pathways. The laminin receptor 6ß4 is one example of an integrin that appears to both promote cell survival and induce apoptosis, depending on the cell type. Bachelder et al. examined how this integrin mediates both responses in various carcinoma cell lines and found that when cells were deficient in the p53 tumor suppressor protein, 6ß4 promoted cell survival through activation of the serine-threonine kinase AKT/Protein Kinase B (PKB). However, when p53 was expressed, activation of this integrin induced apoptosis instead. AKT/PKB inactivation occurred, in the presence of p53, through cleavage events that were initiated by caspase 3, an enzyme implicated in other p53-dependent apoptotic pathways. These findings suggest the contradictory functions of 6ß4 may be associated with the presence of p53. Hence, it is possible that AKT/PKB is a mechanistic link in some cell types between tumor suppressor function and integrin signaling.

Bachelder, R.E., Ribick, M.J., Marchetti, A., Falcioni, R., Soddu, S., Davis, K.R., and Mercurio, A.M. (1999) p53 inhibits 6ß4 integrin survival signaling by promoting the caspase 3-dependent cleavage of AKT/PKB. J. Cell Biol. 147: 1063-1072. [Abstract] [Full Text]