CLEAVAGE OF POLY(ADP-RIBOSE) POLYMERASE BY A PROTEINASE WITH PROPERTIES LIKE ICE

RECENT studies suggest that proteases of the interleukin 1-beta-conver ting enzyme (ICE)/ced-3 family are involved in initiating the active p hase of apoptosis(1-3). Here we identify a novel protease resembling I CE (prICE) that is active in a cell-free system that reproduces the mo rphological and biochemical events of apoptosis(4). prICE cleaves the nuclear enzyme poly(ADP-ribose) polymerase (PARP) at a tetrapeptide se quence identical to one of two ICE sites in pro-interleukin-1-beta. Ho wever, prICE does not cleave purified pro-interleukin-1-beta, and puri fied ICE does not cleave PARP, indicating that the two activities are distinct. Inhibition of prICE abolishes all manifestations of apoptosi s in the extracts including morphological changes, cleavage of PARP an d production of an oligonucleosomal ladder. These studies suggest that prICE might be pivotal in initiating the active phase of apoptosis in vitro and in intact cells.