Mitochondrial Translocation of Protein Kinase C δ in Phorbol Ester-induced Cytochrome c Release and Apoptosis

doi:10.1074/jbc.C000048200

Mitochondrial Translocation of Protein Kinase C δ in Phorbol Ester-induced Cytochrome c Release and Apoptosis*

From the Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 and the ^‡Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87115

Abstract

Apoptosis is induced by the release of cytochromec from mitochondria to the cytoplasm. The present studies demonstrate that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces translocation of protein kinase C (PKC) δ from the cytoplasm to mitochondria. The results also show that translocation of PKCδ results in release of cytochrome c. The functional significance of this event is further supported by the demonstration that PKCδ translocation is required for TPA-induced apoptosis. These findings demonstrate that translocation of PKCδ to mitochondria is responsible, at least in part, for inducing cytochrome crelease and apoptosis.

Footnotes

↵* This work was supported by Public Health Service Grants CA42802 (to D. K.) and GM58200 (to R. D.) awarded by the NCI, DHHS and by Charlotte Geyer Foundation Grant 9219401 (to S. K.).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.
↵§ To whom correspondence should be addressed. Tel.: 617-632-3141; Fax: 617-632-2934; E-mail: donald_kufe@dfci.harvard.edu.
Published, JBC Papers in Press, May 18, 2000, DOI 10.1074/jbc.C000048200
↵2 P. K. Majumder, P. Pandey, X. Sun, K. Cheng, R. Datta, S. Saxena, S. Kharbanda, and D. Kufe, unpublished data.
Abbreviations:

PKC

protein kinase C

TPA

12-0-tetradecanoylphorbol-13-acetate

DAG

diacylglycerol

PLC

phospholipase C

DOG

1,2-dioctanoyl-sn-glycerol

PBS

phosphate-buffered saline

GFP

green fluorescence protein

PAGE

polyacrylamide gel electrophoresis

RD

regulatory domain
- Received January 20, 2000.
- Revision received May 12, 2000.
The American Society for Biochemistry and Molecular Biology, Inc.