EVIDENCE FOR AN INTERLEUKIN-1-BETA CONVERTING-ENZYME (ICE)-LIKE ACTIVITY DISTINCT FROM ICE AND RESPONSIBLE FOR ICE AND CPP32 CLEAVAGE DURING APOPTOSIS

IL-1 beta converting enzyme (ICE) and ICE-related proteases (IRPs) hav e been suggested to play a central role in apoptosis, We report the us e of peptidic ICE inhibitors to reassess the role of this enzyme in th e apoptosis induced by Fas or TNF alpha receptor ligation in Jurkat ce lls, U937 cells or monocytes, Our results show that inhibition of IL-1 beta processing can be dissociated from inhibition of apoptosis, Inde ed, two out of three compounds active on ICE are not inhibitory for ap optosis, This shows that ICE is not required for progression in the ap optotic pathway, but that one or several IRPs are necessary, In additi on, Western blot analysis of cell lysates shows that both ICE and CPP3 2 precursors disappear rapidly after apoptosis induction, while ICH-1( L) precursor remains intact, Concomitant appearance of cleavage produc ts can be visualized for CPP32, but not for ICE, suggesting that the f ormer is proteolytically activated, In addition, this precursor cleava ge can be blocked by an ICE inhibitor active on apoptosis, Altogether, our data support the hypothesis that one or several IRPs are necessar y for apoptosis and are responsible for ICE and CPP32 cleavage during this process.