Oncotarget

Research Papers:

Mps1 is SUMO-modified during the cell cycle

Agnese Restuccia, Feikun Yang, Changyan Chen, Lou Lu and Wei Dai _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:3158-3170. https://doi.org/10.18632/oncotarget.6552

Metrics: PDF 892 views  |   HTML 895 views  |   ?  


Abstract

Agnese Restuccia1,*, Feikun Yang2,*, Changyan Chen3, Lou Lu4, Wei Dai2

1Division of Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany

2Departments of Environmental Medicine, Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, Tuxedo Park, NY, USA

3Center for Drug Discovery, Northeastern University, Boston, MA, USA

4Division of Molecular Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Torrance, CA, USA

*These authors contributed equally to this work

Correspondence to:

Wei Dai, e-mail: wei.dai@nyumc.org

Keywords: Mps1, mitosis, sumoylation, BubR1

Received: August 24, 2015     Accepted: November 21, 2015     Published: December 10, 2015

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 6552