Inhibition of Bcl-2-dependent cell survival by a caspase inhibitor: a possible new pathway for Bcl-2 to regulate cell death

The REtsAF cell line expresses a temperature-sensitive mutant of the SV40 l arge tumor antigen. At restrictive temperature (39.5 degrees C), the cells undergo p53-mediated apoptosis, which can be inhibited by Bcl-2, Here, we s how that Z-VAD-fmk, a caspase inhibitor, can suppress the Bcl-2-dependent c ell survival at 39.5 degrees C. This result suggests that a caspase-like ac tivity can act as an inhibitor of apoptosis in this model, downstream of Bc l-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, (C) 1999 Federation of European Biochemical Societies.