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

Vincent Rincheval (1) , Flore Renaud (1) , Christophe Lemaire (1) , Nelly Godefroy (1) , Pascale Trotot (1) , Viviane Boulo (2) , Bernard Mignotte (1) , Jean-Luc Vayssière (1)

1 LGBC - Laboratoire de génétique et biologie cellulaire
2 IGR - Institut Gustave Roussy

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.

Mots clés: bcl-2; Senescence; Apoptosis; Cell cycle; senescence; apoptosis; cell cycle; bcl-2

Domaines: Sciences du Vivant [q-bio]

Vincent Rincheval, Flore Renaud, Christophe Lemaire, Nelly Godefroy, Pascale Trotot, et al.. Bcl-2 can promote p53-dependent senescence versus apoptosis without affecting the G1/S transition. Biochemical and Biophysical Research Communications, 2002, 298 (2), pp.282-288. ⟨10.1016/S0006-291X(02)02454-3⟩. ⟨hal-03002751⟩