Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells
Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells
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DOI：
10.1128/mcb.00018-07
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发表时间：
2007-12-01
影响因子：
5.3
通讯作者：
Kim, Kyong-Tai
中科院分区：
文献类型：
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作者：
Kang, Tae-Hong;Park, Do-Young;Kim, Kyong-Tai
有丝分裂染色质凝聚是真核生物细胞分裂所必需的。组蛋白N-末端尾的翻译后修饰，特别是有丝分裂组蛋白激酶的磷酸化，可能促进这一过程。在哺乳动物中，极光B被认为是有丝分裂组蛋白H3 Ser 10激酶;然而，单独使用极光B不足以磷酸化H3 Ser 10。我们发现组蛋白H3被牛痘相关激酶1（VRK 1）磷酸化。VRK 1可直接磷酸化H3中的Thr 3和Ser 10。VRK 1活性的丧失与有丝分裂过程中H3磷酸化的显著降低有关。VRK 1对Ser 10的磷酸化作用与aurora B类似。此外，VRK 1的表达和染色质定位依赖于细胞周期时相。VRK 1的过表达导致细胞核的显著浓缩。我们的研究结果共同支持VRK 1作为一种新型的有丝分裂组蛋白H3激酶在哺乳动物中的作用。
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.