Bcl-2 can promote p53-dependent senescence versus apoptosis without affecting the G1/S transition Article - 2002

Vincent Rincheval, Flore Renaud, Christophe Lemaire, Nelly Godefroy, Pascale Trotot, Viviane Boulo, Bernard Mignotte, Jean-Luc Vayssière

Vincent Rincheval, Flore Renaud, Christophe Lemaire, Nelly Godefroy, Pascale Trotot, Viviane Boulo, Bernard Mignotte, Jean-Luc Vayssière, « Bcl-2 can promote p53-dependent senescence versus apoptosis without affecting the G1/S transition  », Biochemical and Biophysical Research Communications, 2002. ISSN 0006-291X

Abstract

With the aim to identify events involved in the determination of p53-dependent apoptosis versus growth arrest, we used rat embryo fibroblasts expressing a temperature-sensitive mutant (tsA58) of the SV40 large tumour antigen (LT). Heat-inactivation of LT leads to p53 activation and commitment to a senescent-like state (REtsA15 cell line) or apoptosis (REtsAF cell line). We report that senescence is associated with high levels of the anti-apoptotic Bcl-2 protein and a cell cycle arrest in G1 phase, whereas ap-optosis is associated with low levels of Bcl-2 and a cell cycle arrest in G2 phase. Here we show that Bcl-2, which can inhibit apoptosis and proliferation, turns the apoptotic phenotype into a senescent-like phenotype in G2 phase. This result suggests that Bcl-2-dependent inhibition of apoptosis could be crucial for the commitment to replicative senescence, whereas its ability to inhibit G1 progression would not be required.

Voir la notice complète sur HAL

Actualités