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Publication : Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage-induced apoptosis.

First Author  Park CH Year  2011
Journal  Mol Biol Cell Volume  22
Issue  8 Pages  1398-408
PubMed ID  21346188 Mgi Jnum  J:182991
Mgi Id  MGI:5317271 Doi  10.1091/mbc.E10-08-0717
Citation  Park CH, et al. (2011) Protein kinase Cdelta regulates vaccinia-related kinase 1 in DNA damage-induced apoptosis. Mol Biol Cell 22(8):1398-408
abstractText  Vaccinia-related kinase 1 (VRK1) is a novel serine/threonine kinase that plays an important role in cell proliferation. However, little is known about the upstream regulators of VRK1 activity. Here we provide evidence for a role of protein kinase Cdelta (PKCdelta) in the regulation of murine VRK1. We show that PKCdelta interacts with VRK1, phosphorylates the Ser-355 residue in the putative regulatory region, and negatively regulates its kinase activity in vitro. Intriguingly, PKCdelta-induced cell death was facilitated by phosphorylation of VRK1 when cells were exposed to a DNA-damaging agent. In addition, p53 played a critical role in the regulation of DNA damage-induced cell death accompanied by PKCdelta-mediated modulation of VRK1. In p53-deficient cells, PKCdelta-mediated phosphorylation of VRK1 had no effect on cell viability. However, cells overexpressing p53 exhibited significant reduction of cell viability when cotransfected with both VRK1 and PKCdelta. Taken together, these results indicate that PKCdelta regulates phosphorylation and down-regulation of VRK1, thereby contributing to cell cycle arrest and apoptotic cell death in a p53-dependent manner.
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