Caspase-3-mediated Cleavage of Protein Kinase C θ in Induction of Apoptosis*
- From the Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
Abstract
Protein kinase C θ (PKCθ) is a member of the novel or nPKC family. A functional role for PKCθ is unknown. The present studies demonstrate that PKCθ is cleaved in the third variable region (V3) in apoptosis induced by diverse agents. PKCθ cleavage is blocked in cells that overexpress the anti-apoptotic Bcl-xL or the baculovirus p35 protein. PKCθ 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 PKCθ fragment, but not full-length PKCθ or a kinase-inactive fragment, results in induction of sub-G1phase DNA, nuclear fragmentation, and lethality. These findings indicate that proteolytic cleavage of PKCθ by Caspase-3 induces events characteristic of apoptosis.
Footnotes
-
↵* This work was supported by United States Public Health Service Grants CA29431 and CA66996 awarded by the National Cancer Institute, DHHS.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are: PKC, protein kinase C (cPKC, classical PKC; nPKC, novel PKC; aPKC, atypical PKC); ICE, interleukin-1β-converting enzyme; Ced, Caenorhabditis elegans death; PARP, poly(ADP-ribose) polymerase; FL, full-length; CF, cleaved fragment; DAPI, 4,6-diamidino-2-phenylindole.
-
- Received May 14, 1997.
