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PLK1 对 CAP-H2 的磷酸化作用在有丝分裂早期通过凝聚素 II 引发染色体凝聚。

Plk1 phosphorylation of CAP-H2 triggers chromosome condensation by condensin II at the early phase of mitosis.

机构信息

Department of Biochemistry, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.

Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

出版信息

Sci Rep. 2017 Jul 17;7(1):5583. doi: 10.1038/s41598-017-05986-7.

Abstract

Condensin complexes play crucial roles in chromosome condensation that is a fundamental process to establish the "rod-like" shape of chromosome structure in mitosis. Failure of the chromosome assembly causes chromosome segregation errors and subsequent genomic instability. However, a molecular mechanism that controls condensin function for the chromosomal organization has not been fully understood. Here, we show that the abundance of CAP-H2, one of the condensin II subunits, is fluctuated during the cell cycle in accordance with Plk1 kinase activity. Inhibition of Plk1 leads to Cdc20-mediated degradation of CAP-H2 in mitosis. Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase. These findings suggest that Plk1 phosphorylation regulates condensin II function by modulating CAP-H2 expression levels to facilitate proper mitotic chromosome organization.

摘要

凝聚素复合物在染色体凝聚中起着至关重要的作用,染色体凝聚是有丝分裂中建立“杆状”染色体结构的基本过程。染色体装配的失败会导致染色体分离错误和随后的基因组不稳定。然而,控制凝聚素功能的分子机制对于染色体组织尚未完全理解。在这里,我们表明,凝聚素 II 亚基之一 CAP-H2 的丰度在细胞周期中根据 Plk1 激酶活性而波动。Plk1 的抑制导致 Cdc20 在有丝分裂中介导 CAP-H2 的降解。Plk1 在 CAP-H2 的 Ser288 上的磷酸化对于 CAP-H2 的积累和前期准确的染色体凝聚是必需的。这些发现表明,Plk1 磷酸化通过调节 CAP-H2 的表达水平来调节凝聚素 II 功能,从而促进有丝分裂染色体的正确组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f037/5514044/19dc0c1cf25f/41598_2017_5986_Fig1_HTML.jpg

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