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First published online 19 August 2008
doi: 10.1242/jcs.026757

Journal of Cell Science 121, 3035-3041 (2008)
Published by The Company of Biologists 2008
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Research Article

VRK1 phosphorylates CREB and mediates CCND1 expression

Tae-Hong Kang, Do-Young Park, Wanil Kim and Kyong-Tai Kim*

Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology (POSTECH), San-31, Hyoja-Dong, Pohang 790-784, Republic of Korea

* Author for correspondence (e-mail: ktk{at}postech.ac.kr)

Accepted 25 June 2008

Vaccinia virus B1 kinase plays a key role in viral DNA replication. The homologous mammalian vaccinia-related kinases (VRKs) are also implicated in the regulation of DNA replication, although direct evidence remains elusive. Here we show that VRK1 regulates cell cycle progression in the DNA replication period by inducing cyclin D1 (CCND1) expression. Furthermore, depletion of VRK1 in human cancer cells reduces the fraction of cells in S phase at a given time. VRK1 specifically enhances activity of the cAMP-response element (CRE) in the CCND1 promoter by facilitating the recruitment of phospho-CREB to this locus. VRK1 phosphorylates CREB at Ser133 in vitro and the expression of a kinase-dead mutant of VRK1 or knockdown of VRK1 using siRNA fails to activate CREB and subsequently activate CRE. Finally, we show that VRK1 is a critical link in the CCND1 gene expression pathway stimulated by Myc overexpression. Our results indicate that VRK1 is a novel regulator of CCND1 expression.

Key words: VRK, CRE, CREB, Myc, CCND1






© The Company of Biologists Ltd 2008