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新型鼠类 Polo 样激酶 5 可响应 DNA 损伤,并定位于核仁。

The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus.

机构信息

Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

出版信息

Nucleic Acids Res. 2010 May;38(9):2931-43. doi: 10.1093/nar/gkq011. Epub 2010 Jan 25.

Abstract

Polo-like kinases (Plk1-4) are emerging as an important class of proteins involved in many aspects of cell cycle regulation and response to DNA damage. Here, we report the cloning of a fifth member of the polo-like kinase family named Plk5. DNA and protein sequence analyses show that Plk5 shares more similarities with Plk2 and Plk3 than with Plk1 and Plk4. Consistent with this observation, we show that mouse Plk5 is a DNA damage inducible gene. Mouse Plk5 protein localizes predominantly to the nucleolus, and deletion of a putative nucleolus localization signal (NoLS) within its N-terminal moiety disrupts its nucleolar localization. Ectopic expression of Plk5 leads to cell cycle arrest in G1, decreased DNA synthesis, and to apoptosis, a characteristic it shares with Plk3. Interestingly, in contrast to mouse Plk5 gene, the sequence of human Plk5 contains a stop codon that produces a truncated protein lacking part of the kinase domain.

摘要

丝氨酸/苏氨酸激酶(Plk1-4)作为一类重要的蛋白,在细胞周期调控和 DNA 损伤反应等多个方面发挥着重要作用。本文报道了丝氨酸/苏氨酸激酶家族的第五个成员 Plk5 的克隆。DNA 和蛋白质序列分析表明,Plk5 与 Plk2 和 Plk3 的相似度高于与 Plk1 和 Plk4 的相似度。观察结果一致表明,鼠 Plk5 是一种 DNA 损伤诱导基因。鼠 Plk5 蛋白主要定位于核仁,其 N 端结构域内的一个假定核仁定位信号(NoLS)缺失会破坏其核仁定位。Plk5 的异位表达会导致细胞周期 G1 期阻滞、DNA 合成减少和细胞凋亡,这与 Plk3 的特征相同。有趣的是,与鼠 Plk5 基因不同,人 Plk5 序列包含一个终止密码子,产生一个缺失激酶结构域部分的截断蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcd4/2875007/3c0d068636c7/gkq011f1.jpg

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