Restuccia Agnese, Yang Feikun, Chen Changyan, Lu Lou, Dai Wei
Division of Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany.
Departments of Environmental Medicine, Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, Tuxedo Park, NY, USA.
Oncotarget. 2016 Jan 19;7(3):3158-70. doi: 10.18632/oncotarget.6552.
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.
Mps1是一种双特异性蛋白激酶，它在有丝分裂过程中调节纺锤体组装检查点，并介导微管与染色体的正确附着。然而，在细胞周期中控制Mps1蛋白水平及其活性的分子机制仍不清楚。鉴于SUMO化在有丝分裂进程中起重要作用，我们研究了Mps1是否被SUMO修饰以及SUMO化是否影响其在有丝分裂中的活性。我们的结果表明，Mps1在非同步化和有丝分裂细胞群体中均被SUMO化。Mps1被SUMO-1和SUMO-2修饰。我们的进一步研究表明，包括K71、K287、K367和K471在内的赖氨酸残基对于Mps1的SUMO化至关重要。SUMO化似乎在介导Mps1的动粒定位中起作用，从而影响正常的有丝分裂进程。此外，Mps1的SUMO抗性突变体与BubR1的相互作用比与野生型对照更有效。综合来看，我们的结果表明Mps1被SUMO修饰，这在有丝分裂过程中调节Mps1功能方面起着至关重要的作用。
