Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells

• Main Authors: Kang, Tae-Hong, Park, Do-Young, Choi, Yoon Ha, Kim, Kyung-Jin, Yoon, Ho Sup, Kim, Kyong-Tai
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2012
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: https://hdl.handle.net/10356/95026; http://hdl.handle.net/10220/8519
• Institution: Nanyang Technological University

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. Phosphory¬lation 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.