SUMOylation Promotes Nuclear Import and Stabilization of Polo-like Kinase 1 to Support Its Mitotic Function.
SUMOylation Promotes Nuclear Import and Stabilization of Polo-like Kinase 1 to Support Its Mitotic Function.
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SUMO 化促进 Polo 样激酶 1 的核输入和稳定，以支持其有丝分裂功能。
DOI：
10.1016/j.celrep.2017.10.085
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发表时间：
2017
期刊：
影响因子：
8.8
通讯作者：
Fu,Zheng
中科院分区：
文献类型：
--
作者：
Wen,Donghua;Wu,Jianguo;Wang,Lei;Fu,Zheng
作为关键的有丝分裂调节因子，polo 样激酶 1 (PLK1) 受到高度协调和多层次的调节。然而，控制 PLK1 活性和功能的途径才刚刚开始被阐明。最近显示 PLK1 可通过翻译后修饰 (PTM) 进行功能调节，包括磷酸化和泛素化。在此，我们报道 SUMO 化在调节 PLK1 有丝分裂功能中起着重要作用。我们发现 Ubc9 在 CDK1/cyclin B 初始磷酸化和激活后被招募到 PLK1。通过体内和体外 SUMO 化测定，PLK1 被鉴定为生理相关的小泛素相关修饰剂 (SUMO) 靶向蛋白，优先由 SUMO-1 修饰。我们进一步表明 PLK1 上的 K492 对于 SUMO 化至关重要。 SUMO 化导致 PLK1 入核并显着增加其蛋白质稳定性，这两者对于正常有丝分裂进展和基因组完整性至关重要。我们的研究结果表明 SUMO 化是控制 PLK1 有丝分裂功能的重要调节机制。
As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report that SUMOylation plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation by CDK1/cyclin B. Byin vivoandin vitroSUMOylation assays, PLK1 was identified as a physiologically relevant small ubiquitin-related modifier (SUMO)-targeted protein, preferentially modified by SUMO-1. We further showed that K492 on PLK1 is essential for SUMOylation. SUMOylation causes PLK1's nuclear import and significantly increases its protein stability, both of which are critical for normal mitotic progression and genomic integrity. Our findings suggest that SUMOylation is an important regulatory mechanism governing PLK1's mitotic function.