PROTEOLYTIC ACTIVATION OF PROTEIN-KINASE-C-DELTA BY AN ICE CED 3-LIKEPROTEASE INDUCES CHARACTERISTICS OF APOPTOSIS/

Recent studies have shown that protein kinase C (PKC) delta is proteol ytically activated at the onset of apoptosis induced by DNA-damaging a gents, tumor necrosis factor, and anti-Fas antibody. However, the rela tionship of PKC delta cleavage to induction of apoptosis is unknown. T he present studies demonstrate that full-length PKC delta is cleaved a t DMQD(330)N to a catalytically active fragment by the cysteine protea se CPP32. The results also demonstrate that overexpression of the cata lytic kinase fragment in cells is associated with chromatin condensati on, nuclear fragmentation, induction of sub-G1 phase DNA and lethality . By contrast, overexpression of full-length PKC delta or a kinase ina ctive PKC delta fragment had no detectable effect. The findings sugges t that proteolytic activation of PKC delta by a CPP32-like protease co ntributes to phenotypic changes associated with apoptosis.