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. |