Abstract:
: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.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Kang TH,Park DY,Kim W,Kim KTdoi
10.1242/jcs.026757subject
Has Abstractpub_date
2008-09-15 00:00:00pages
3035-41issue
Pt 18eissn
0021-9533issn
1477-9137pii
jcs.026757journal_volume
121pub_type
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更新日期:2001-10-01 00:00:00
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