Mitotic Phosphorylation of SENP3 Regulates DeSUMOylation of Chromosome-Associated Proteins and Chromosome Stability.
Mitotic Phosphorylation of SENP3 Regulates DeSUMOylation of Chromosome-Associated Proteins and Chromosome Stability.
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DOI：
10.1158/0008-5472.can-17-2288
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发表时间：
2018-05
期刊：
影响因子：
11.2
通讯作者：
Bo Wei;Chao Huang;Bin Liu;Yang Wang;Nansong Xia;Qiuju Fan;Guoqiang Chen;Jinke Cheng
中科院分区：
文献类型：
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作者：
Bo Wei;Chao Huang;Bin Liu;Yang Wang;Nansong Xia;Qiuju Fan;Guoqiang Chen;Jinke Cheng
有丝分裂细胞周期的进展和染色体的凝聚和分离是由翻译后的蛋白质修饰如磷酸化和sumo化控制的。然而，SUMO异肽酶（SENP）如何调节细胞有丝分裂过程在很大程度上是未知的。在这里，我们证明了在有丝分裂过程中SENP3的精确磷酸化抑制了SENP3对染色体相关蛋白（包括拓扑异构酶IIα (TopoIIα)）的去氧酰基化活性。细胞周期蛋白b依赖性激酶1和蛋白磷酸酶1α分别被鉴定为控制有丝分裂SENP3磷酸化的激酶和磷酸酶。SENP3磷酸化降低了其与TopoIIα的相互作用，导致SENP3对TopoIIα的deSUMOylation活性降低。此外，我们观察到在表达非磷酸化SENP3突变体的细胞中，有丝分裂停止，染色体不稳定性增加，肿瘤发生促进。这些数据表明，在有丝分裂中，SENP3磷酸化在调节染色体相关蛋白的SUMOylation和染色体稳定性中起着至关重要的作用。意义：SENP3的磷酸化调节染色体相关蛋白的SUMOylation，以维持有丝分裂期间基因组的稳定性。癌症Res;78 (9);2171 - 8。AACR©2018。
Progression of mitotic cell cycle and chromosome condensation and segregation are controlled by posttranslational protein modifications such as phosphorylation and SUMOylation. However, how SUMO isopeptidases (SENP) regulate cell mitotic procession is largely unknown. Here, we demonstrate that precise phosphorylation of SENP3 during mitosis suppresses SENP3 deSUMOylation activity towards chromosome-associated proteins, including topoisomerase IIα (TopoIIα). Cyclin B-dependent kinases 1 and protein phosphatase 1α were identified as the kinase and phosphatase in control of mitotic SENP3 phosphorylation, respectively. SENP3 phosphorylation decreased its interaction with TopoIIα, resulting in reduced SENP3 deSUMOylation activity on TopoIIα. Furthermore, we observed mitotic arrest, increased chromosome instability, and promotion of tumorigenesis in cells expressing a nonphosphorylatable SENP3 mutant. These data show that SENP3 phosphorylation plays a crucial role in regulating the SUMOylation of chromosome-associated proteins and chromosome stability in mitosis.Significance: Phosphorylation of SENP3 regulates SUMOylation of chromosome-associated proteins to maintain genomic stability during mitosis. Cancer Res; 78(9); 2171-8. ©2018 AACR.