Proteolytic Activation of Protein Kinase C {delta} by an ICE/CED 3-like Protease Induces Characteristics of Apoptosis

doi:10.1084/jem.184.6.2399

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© The Rockefeller University Press, 0022-1007/1996/12/2399/ $5.00
The Journal of Experimental Medicine, Volume 184, Number 6, December 1, 1996 2399-2404

Brief Definitive Reports

Proteolytic Activation of Protein Kinase C ${delta}$ by an ICE/CED 3-like Protease Induces Characteristics of Apoptosis

Tariq Ghayur^*, Margaret Hugunin^*, Robert V. Talanian^*, Sheldon Ratnofsky^*, Christopher Quinlan^*, Yutaka Emoto, Pramod Pandey, Rakesh Datta, Yinyin Huang, Surender Kharbanda, Hamish Allen^*, Robert Kamen^*, Winnie Wong^*, and Donald Kufe

From ^* BASF Bioresearch Corporation, Worcester, Massachusetts 01605; and Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

Recent studies have shown that protein kinase C (PKC) ${delta}$ is proteolyticallyactivated at the onset of apoptosis induced by DNA-damagingagents, tumor necrosis factor, and anti-Fas antibody. However,the relationship of PKC ${delta}$ cleavage to induction of apoptosis isunknown. The present studies demonstrate that full-length PKC ${delta}$ is cleaved at DMQD₃₃₀N to a catalytically active fragment bythe cysteine protease CPP32. The results also demonstrate thatoverexpression of the catalytic kinase fragment in cells isassociated with chromatin condensation, nuclear fragmentation,induction of sub-G1 phase DNA and lethality. By contrast, overexpressionof full-length PKC ${delta}$ or a kinase inactive PKC ${delta}$ fragment had nodetectable effect. The findings suggest that proteolytic activationof PKC ${delta}$ by a CPP32-like protease contributes to phenotypic changesassociated with apoptosis.

Address correspondence to Donald W. Kufe, Division of CancerPharmacology, Dana-Farber Cancer Institute, 44 Binney St., Boston,MA 02115.

This investigation was supported by Public Health Service grantsCA66996, CA55241, and CA29431 awarded by the National CancerInstitute, DHHS.

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