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Inhibition of Bcl-2-dependent cell survival by a caspase inhibitor: a possible new pathway for Bcl-2 to regulate cell death.
Authors:V Rincheval  F Renaud  C Lemaire  B Mignotte  J L Vayssière
Affiliation:Université de Versailles/St Quentin-en-Yvelines, UPRESA-CNRS 8087, Laboratoire génome, cellule et informatique, 45 avenue des Etats-Unis, 78035, Versailles, France.
Abstract:The REtsAF cell line expresses a temperature-sensitive mutant of the SV40 large tumor antigen. At restrictive temperature (39.5 degrees C), the cells undergo p53-mediated apoptosis, which can be inhibited by Bcl-2. Here, we show that Z-VAD-fmk, a caspase inhibitor, can suppress the Bcl-2-dependent cell survival at 39.5 degrees C. This result suggests that a caspase-like activity can act as an inhibitor of apoptosis in this model, downstream of Bcl-2. Our results also suggest that this activity may be up-regulated by Bcl-2 and may be responsible for cleavage of the tumor suppressor Rb protein.
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