title: Bcl-2 can promote p53-dependent senescence versus apoptosis without affecting the G1/S transition.
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 apoptosis 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.
authors.affiliation: Laboratoire de génétique et biologie cellulaire, Université de Versailles/St. Quentin-en-Yvelines, UPRESA-CNRS 8087, 45 avenue des Etats-Unis, Versailles cedex 78035, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Rincheval
authors.forename: Flore
authors.initials: F
authors.lastname: Renaud
authors.forename: Christophe
authors.initials: C
authors.lastname: Lemaire
authors.forename: Nelly
authors.initials: N
authors.lastname: Godefroy
authors.forename: Pascale
authors.initials: P
authors.lastname: Trotot
authors.forename: Viviane
authors.initials: V
authors.lastname: Boulo
authors.forename: Bernard
authors.initials: B
authors.lastname: Mignotte
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vayssière
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D016922:Cellular Senescence; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016193:G1 Phase; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016196:S Phase; D013696:Temperature; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA