Volume 272, Number 33, Issue of August 15, 1997 pp. 20317-20320
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
Caspase-3-mediated Cleavage of Protein Kinase C  in Induction of Apoptosis

(Received for publication, May 14, 1997)

From the Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

Protein kinase C  (PKC) is a member of the novel or nPKC family. A functional role for PKC is unknown. The present studies demonstrate that PKC is cleaved in the third variable region (V3) in apoptosis induced by diverse agents. PKC cleavage is blocked in cells that overexpress the anti-apoptotic Bcl-x_L or the baculovirus p35 protein. PKC is cleaved by Caspase-3 and by apoptotic cell lysates at a DEVD₃₅₄/K site. We also show that overexpression of the cleaved kinase-active PKC fragment, but not full-length PKC or a kinase-inactive fragment, results in induction of sub-G₁ phase DNA, nuclear fragmentation, and lethality. These findings indicate that proteolytic cleavage of PKC by Caspase-3 induces events characteristic of apoptosis.

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