Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells.
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.
Kang
Tae-Hong
TH
Department of Life Science, Division of Molecular & Life Science, Pohang University of Science and Technology, San-31, Hyoja-Dong, Pohang 790-784, Republic of Korea.
Park
Do-Young
DY
Choi
Yoon Ha
YH
Kim
Kyung-Jin
KJ
Yoon
Ho Sup
HS
Kim
Kyong-Tai
KT
D000818:Animals; D002453:Cell Cycle; D002467:Cell Nucleus / Q000201:enzymology; D002843:Chromatin / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats
D002843:Chromatin; D006657:Histones; D010769:Phosphothreonine; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases