Protein Kinase Cδ Regulates Vaccinia-related Kinase 1 in DNA Damage-induced Apoptosis

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2011 Feb 25

PMID 21346188

Citations 8

Authors

Choon-Ho Park

Bo-Hwa Choi

Min-Woo Jeong

Sangjune Kim

Wanil Kim

Yun Seon Song

Kyong-Tai Kim

Affiliations

Soon will be listed here.

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.

Citing Articles

Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis.

Cartwright T, Harris R, Meyer S, Mon A, Watson N, Tan C Sci Rep. 2022; 12(1):11210.

PMID: 35778595 PMC: 9249732. DOI: 10.1038/s41598-022-15339-8.

VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes.

Martin-Doncel E, Rojas A, Cantarero L, Lazo P Sci Rep. 2019; 9(1):13381.

PMID: 31527692 PMC: 6746721. DOI: 10.1038/s41598-019-49821-7.

Lysophosphatidic acid receptor 1 antagonist ki16425 blunts abdominal and systemic inflammation in a mouse model of peritoneal sepsis.

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PMID: 25701366 PMC: 4458421. DOI: 10.1016/j.trsl.2015.01.008.

Luteolin suppresses cancer cell proliferation by targeting vaccinia-related kinase 1.

Kim Y, Kim S, Shin J, Harikishore A, Lim J, Jung Y PLoS One. 2014; 9(10):e109655.

PMID: 25310002 PMC: 4195671. DOI: 10.1371/journal.pone.0109655.

Serine phosphorylation is critical for the activation of ubiquitin-specific protease 1 and its interaction with WD40-repeat protein UAF1.

Villamil M, Liang Q, Chen J, Choi Y, Hou S, Lee K Biochemistry. 2012; 51(45):9112-23.

PMID: 23116119 PMC: 3617561. DOI: 10.1021/bi300845s.

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