Acinus-provoked protein kinase C delta isoform activation is essential for apoptotic chromatin condensation.
Histone H2B phosphorylation tightly correlates with chromatin condensation during apoptosis. The caspase-cleaved acinus (apoptotic chromatin condensation inducer in the nucleus) provokes chromatin condensation in the nucleus, but the molecular mechanism accounting for this effect remains elusive. Here, we report that the active acinus p17 fragment initiates H2B phosphorylation and chromatin condensation by activating protein kinase C delta isoform (PKC-delta). We show that p17 binds to both Mst1 and PKC-delta, which is upregulated by apoptotic stimuli, enhancing their kinase activities. Acinus mutant susceptible to degradation elicits stronger chromatin condensation and higher H2B phosphorylation than wild-type acinus. Dominant-negative PKC-delta but not Mst1 robustly blocks acinus-initiated H2B phosphorylation. Surprisingly, depletion of Mst1 triggers caspase-3 activation, provoking H2B phosphorylation through activating PKC-delta. Further, acinus-elicited H2B phosphorylation and chromatin condensation are abrogated in PKC-delta-deficient mouse embryonic fibroblast cells and siRNA-knocked down PC12 cells. Thus, PKC-delta but not Mst1 acts as a physiological downstream kinase of acinus in promoting H2B phosphorylation and chromatin condensation.
Hu
Y
Y
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Liu
Z
Z
Yang
S-J
SJ
Ye
K
K
D000818:Animals; D017209:Apoptosis; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004789:Enzyme Activation; D005799:Genes, Dominant; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D051745:Protein Kinase C-delta / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats
D002843:Chromatin; D006657:Histones; D007527:Isoenzymes; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D010768:Phosphoserine; D017228:Hepatocyte Growth Factor; D051745:Protein Kinase C-delta