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Molecular and Cellular Biology, December 2007, p. 8533-8546, Vol. 27, No. 24
0270-7306/07/$08.00+0 doi:10.1128/MCB.00018-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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Department of Life Science, Division of Molecular & Life Science, Pohang University of Science and Technology (POSTECH), San-31, Hyoja-Dong, Pohang 790-784, Republic of Korea,1 X-Ray Research Group, Pohang Accelerator Laboratory, Pohang 790-784, Republic of Korea,2 Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore3
Received 4 January 2007/ Returned for modification 13 March 2007/ Accepted 25 September 2007
Mitotic chromatin condensation is essential for cell division in eukaryotes. Posttranslational modification of the N-terminal tail of histone proteins, particularly by phosphorylation by mitotic histone kinases, may facilitate this process. In mammals, aurora B is believed to be the mitotic histone H3 Ser10 kinase; however, it is not sufficient to phosphorylate H3 Ser10 with aurora B alone. We show that histone H3 is phosphorylated by vaccinia-related kinase 1 (VRK1). Direct phosphorylation of Thr3 and Ser10 in H3 by VRK1 both in vitro and in vivo was observed. Loss of VRK1 activity was associated with a marked decrease in H3 phosphorylation during mitosis. Phosphorylation of Ser10 by VRK1 is similar to that by aurora B. Moreover, expression and chromatin localization of VRK1 depended on the cell cycle phase. Overexpression of VRK1 resulted in a dramatic condensation of nuclei. Our findings collectively support a role of VRK1 as a novel mitotic histone H3 kinase in mammals.
Published ahead of print on 15 October 2007.
Supplemental material for this article may be found at http://mcb.asm.org/.
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