Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis.
Recent studies have shown that protein kinase C (PKC) delta is proteolytically activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. However, the relationship of PKC delta cleavage to induction of apoptosis is unknown. The present studies demonstrate that full-length PKC delta is cleaved at DMQD330N to a catalytically active fragment by the cysteine protease CPP32. The results also demonstrate that overexpression of the catalytic kinase fragment in cells is associated with chromatin condensation, nuclear fragmentation, induction of sub-G1 phase DNA and lethality. By contrast, overexpression of full-length PKC delta or a kinase inactive PKC delta fragment had no detectable effect. The findings suggest that proteolytic activation of PKC delta by a CPP32-like protease contributes to phenotypic changes associated with apoptosis.
Ghayur
T
T
BASF Bioresearch Corporation, Worcester, Massachusetts 01605, USA.
Hugunin
M
M
Talanian
R V
RV
Ratnofsky
S
S
Quinlan
C
C
Emoto
Y
Y
Pandey
P
P
Datta
R
R
Huang
Y
Y
Kharbanda
S
S
Allen
H
H
Kamen
R
R
Wong
W
W
Kufe
D
D
D000595:Amino Acid Sequence; D017209:Apoptosis; D029742:Caenorhabditis elegans Proteins; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D007527:Isoenzymes; D010446:Peptide Fragments; D011994:Recombinant Proteins; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1