PKC-delta is an apoptotic lamin kinase

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• The nuclear lamina disassembles during apoptosis, a process involving lamin protein degradation by caspase 6.
• The role of protein phosphorylation in apoptotic nuclear lamina disassembly, distinct from mitotic processes, remains unclear.
• Protein kinase C-delta (PKC-delta) is activated by caspase 3 during apoptosis and its kinase fragment can induce apoptotic nuclear changes.

Purpose of the Study:

• To investigate the role of PKC-delta in the disassembly of the nuclear lamina during apoptosis.
• To determine if PKC-delta directly phosphorylates lamin proteins as part of the apoptotic process.

Main Methods:

• Co-localization studies of PKC-delta and lamin B during apoptosis.
• Assessment of lamin B phosphorylation and proteolysis in the presence and absence of PKC-delta inhibitors.
• In vitro phosphorylation assays using recombinant human PKC-delta and lamin B.

Main Results:

• PKC-delta co-localized with lamin B during apoptosis, and its activation by caspase 3 correlated with lamin B phosphorylation and proteolysis.
• Inhibition of PKC-delta delayed lamin proteolysis, even with active caspase 6, while mitotic lamin kinase inhibitors had no effect.
• Recombinant PKC-delta directly phosphorylated lamin B in vitro, indicating a direct action.

Conclusions:

• PKC-delta functions as an apoptotic lamin kinase, directly phosphorylating lamin B.
• Efficient nuclear lamina disassembly during apoptosis requires both PKC-delta-mediated hyperphosphorylation and caspase-mediated proteolysis of lamins.
• PKC-delta plays a direct and essential role in the apoptotic pathway of nuclear lamina disassembly.