Abstract
Protein kinase C-δ is activated during apoptosis, following proteolytic cleavage by caspase 3. Furthermore, overexpression of the catalytic kinase fragment of PKC-δ 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-δ 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-δ co-localized with lamin B during apoptosis and activation of PKC-δ by caspase 3 was concomitant with lamin B phosphorylation and proteolysis. Inhibition of PKC-δ 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-δ was able to phosphorylate lamin B in vitro suggesting that its actions are direct and not via an intermediary kinase. We propose that PKC-δ is an apoptotic lamin kinase and that efficient lamina disassembly at apoptosis requires both lamin hyperphosphorylation and caspase mediated proteolysis.
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Acknowledgements
We are grateful to Dr N Chaudhary for the gift of the lamin antibodies and to Professor D Kufe for the GFP-tagged PKC-δ constructs. We thank Mike Salmon and Nick Henriquez for helpful discussion of the manuscript. This work was supported by grants from the Leukaemia Research Fund (T Cross and E Deacon), the MRC (G Griffiths) and The Royal Society (JM Lord).
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Cross, T., Griffiths, G., Deacon, E. et al. PKC-δ is an apoptotic lamin kinase. Oncogene 19, 2331–2337 (2000). https://doi.org/10.1038/sj.onc.1203555
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DOI: https://doi.org/10.1038/sj.onc.1203555
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