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 apopto sis, 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 protei ns are degraded by caspase 6 and the contribution made by phosphorylation h as not been proven. We show here that protein kinase C-delta co-localized w ith lamin B during apoptosis and activation of PKC-delta by caspase 3 was c oncomitant 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 ill vitro su ggesting that its actions are direct and not via an intermediary kinase. We propose that PKC-delta is an apoptotic lamin kinase and that efficient lam ina disassembly at apoptosis requires both lamin hyperphosphorylation and c aspase mediated proteolysis.