EVIDENCE AGAINST A FUNCTIONAL SITE FOR BCL-2 DOWNSTREAM OF CASPASE CASCADE IN PREVENTING APOPTOSIS

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.