IDENTIFICATION AND INHIBITION OF THE ICE CED-3 PROTEASE NECESSARY FORMAMMALIAN APOPTOSIS/

The protease responsible for the cleavage of poly(ADP-ribose) polymera se and necessary for apoptosis has been purified and characterized. Th is enzyme, named apopain, is composed of two subunits of relative mole cular mass (M(r)) 17K and 12K that are derived from a common proenzyme identified as CPP32. This proenzyme is related to interleukin-1 beta- converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans. A potent peptide alde hyde inhibitor has been developed and shown to prevent apoptotic event s In vitro, suggesting that apopain/CPP32 is important for the initiat ion of apoptotic cell death.