PKC-delta is an apoptotic lamin kinase.
Protein kinase C-delta is activated during apoptosis, following proteolytic cleavage by caspase 3. Furthermore, overexpression of the catalytic kinase fragment of PKC-delta induces the nuclear phenotype associated with apoptosis, though the molecular basis of this effect has not been determined. In these studies we have examined the role of PKC-delta in the disassembly of the nuclear lamina at apoptosis. The nuclear lamina is disassembled during mitosis and apoptosis and mitotic disassembly involves hyperphosphorylation of lamin proteins by mitotic lamin kinases. During apoptosis, lamin proteins are degraded by caspase 6 and the contribution made by phosphorylation has not been proven. We show here that protein kinase C-delta co-localized with lamin B during apoptosis and activation of PKC-delta by caspase 3 was concomitant with lamin B phosphorylation and proteolysis. Inhibition of PKC-delta delayed lamin proteolysis, even in the presence of active caspase 6, whilst inhibitors of mitotic lamin kinases were without effect. In addition recombinant human PKC-delta was able to phosphorylate lamin B in vitro suggesting that its actions are direct and not via an intermediary kinase. We propose that PKC-delta is an apoptotic lamin kinase and that efficient lamina disassembly at apoptosis requires both lamin hyperphosphorylation and caspase mediated proteolysis.
Cross
T
T
MRC Centre for Immune Regulation, University of Birmingham, UK.
Griffiths
G
G
Deacon
E
E
Sallis
R
R
Gough
M
M
Watters
D
D
Lord
J M
JM
D000098:Acetophenones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001578:Benzopyrans / Q000494:pharmacology; D001692:Biological Transport; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051745:Protein Kinase C-delta
D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D003561:Cytarabine; C085746:rottlerin; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases