Mps1 is SUMO-modified during the cell cycle

被引：10

作者：

Restuccia, Agnese ^{[1
]}

Yang, Feikun ^{[2
,3
]}

Chen, Changyan ^{[4
]}

Lu, Lou ^{[5
]}

Dai, Wei ^{[2
,3
]}

机构：

[1] German Canc Res Ctr, Div Virus Associated Carcinogenesis, Heidelberg, Germany

[2] NYU, Langone Med Ctr, Dept Environm Med, Tuxedo Pk, NY USA

[3] NYU, Langone Med Ctr, Dept Mol Pharmacol & Biochem, Tuxedo Pk, NY USA

[4] Northwestern Univ, Ctr Drug Discovery, Boston, MA USA

[5] Univ Calif Los Angeles, Dept Med, Div Mol Med, David Geffen Sch Med, Torrance, CA USA

来源：

ONCOTARGET | 2016年 / 7卷 / 03期

关键词：

Mps1; mitosis; sumoylation; BubR1; SPINDLE ASSEMBLY CHECKPOINT; MITOTIC CHECKPOINT; KINETOCHORE LOCALIZATION; CENTROSOME DUPLICATION; HELA-CELLS; AURORA-B; CENP-E; KINASE; BUBR1; MITOSIS;

D O I：

10.18632/oncotarget.6552

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mps1 is a dual specificity protein kinase that regulates the spindle assembly checkpoint and mediates proper microtubule attachment to chromosomes during mitosis. However, the molecular mechanism that controls Mps1 protein level and its activity during the cell cycle remains unclear. Given that sumoylation plays an important role in mitotic progression, we investigated whether Mps1 was SUMO-modified and whether sumoylation affects its activity in mitosis. Our results showed that Mps1 was sumoylated in both asynchronized and mitotic cell populations. Mps1 was modified by both SUMO-1 and SUMO-2. Our further studies revealed that lysine residues including K71, K287, K367 and K471 were essential for Mps1 sumoylation. Sumoylation appeared to play a role in mediating kinetochore localization of Mps1, thus affecting normal mitotic progression. Furthermore, SUMO-resistant mutants of Mps1 interacted with BubR1 more efficiently than it did with the wild-type control. Combined, our results indicate that Mps1 is SUMO-modified that plays an essential role in regulating Mps1 functions during mitosis.

引用

页码：3158 / 3170

页数：13

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