title: Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage-induced apoptosis.
abstract: 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 Cδ (PKCδ) in the regulation of murine VRK1. We show that PKCδ interacts with VRK1, phosphorylates the Ser-355 residue in the putative regulatory region, and negatively regulates its kinase activity in vitro. Intriguingly, PKCδ-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 PKCδ-mediated modulation of VRK1. In p53-deficient cells, PKCδ-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 PKCδ. Taken together, these results indicate that PKCδ regulates phosphorylation and down-regulation of VRK1, thereby contributing to cell cycle arrest and apoptotic cell death in a p53-dependent manner.
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang, Korea.
authors.forename: Choon-Ho
authors.initials: CH
authors.lastname: Park
authors.forename: Bo-Hwa
authors.initials: BH
authors.lastname: Choi
authors.forename: Min-Woo
authors.initials: MW
authors.lastname: Jeong
authors.forename: Sangjune
authors.initials: S
authors.lastname: Kim
authors.forename: Wanil
authors.initials: W
authors.lastname: Kim
authors.forename: Yun Seon
authors.initials: YS
authors.lastname: Song
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects; D018274:Electroporation; D004926:Escherichia coli; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D009154:Mutation; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D012694:Serine; D005047:Etoposide; D017346:Protein Serine-Threonine Kinases; C484518:Vrk1 protein, mouse; D051745:Protein Kinase C-delta