CASPASE-3 CPP32-LIKE ACTIVITY IS NOT SUFFICIENT TO MEDIATE APOPTOSIS IN AN IL-2 DEPENDENT T-CELL LINE/

CTLL cells undergo apoptosis when cultured in the absence of IL-2, The IL-1 beta-converting-enzyme (ICE)/caspase family has been implicated as an integral component of some forms of apoptosis, Numerous members of the caspase family have been identified, and it appears as if caspa se-3/CPP32 plays a critical role, Previously we demonstrated that ICE/ caspase-1 expression increases in CTLL cells during apoptosis; however , inhibition of ICE activity did not abrogate apoptotic death, The pur pose of this report is to determine if other members of the caspase fa mily are involved in T cell apoptosis induced by growth factor starvat ion, We show that cytosolic CPP32-like activity, as measured by the cl eavage of DEVD-pNA and poly(ADP-ribose) polymerase (PARP), increases d uring apoptosis following growth factor deprivation. Cytosolic CPP32-l ike activity is inhibited in cells treated with the broad spectrum ICE family inhibitor boc-aspartyl(OMe)-fluoromethylketone (D-FMK) and by VAD-FMK and DEVD-FMK which have greater specificity for CPP32-like ICE homologs; however, only the broad spectrum ICE inhibitor D-FMK inhibi ted apoptosis, Our results suggest that apoptosis induced by growth fa ctor deprivation involves the caspase family, but increased CPP32-like activity is not sufficient to mediate apoptosis induced by IL-2 starv ation.