N. Yasuhara et al., EVIDENCE AGAINST A FUNCTIONAL SITE FOR BCL-2 DOWNSTREAM OF CASPASE CASCADE IN PREVENTING APOPTOSIS, Oncogene, 15(16), 1997, pp. 1921-1928
Apoptotic cell death is driven by ICE family proteases (caspases) and
negatively regulated by Bcl-2 family proteins. Although it has been sh
own that Bcl-2 exerts anti-apoptotic activity by blocking a step(s) le
ading to the activation of caspases, a role for Bcl-2 and Bcl-x(L) dow
nstream of the caspase cascade has remained unclear. Here, we show tha
t purified active caspase-3 (CPP32/Yama/apopain) and caspase-1 (ICE) i
nduces apoptosis when microinjected into the cytoplasm of cells, confi
rming our recent observations, and that the apoptosis is not at all pr
evented by Bcl-2 and Bcl-x(L), which are overexpressed more than suffi
ciently to prevent Fas-mediated and overexpressed procaspase-1-mediate
d apoptosis. Thus, Bcl-2 and Bcl-x(L) do not act downstream of the cas
pase cascade.