Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
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Mourad Sanhaji1*, Andreas Ritter1, Hannah R. Belsham2, Claire T. Friel2, Susanne Roth1, Frank Louwen1 and Juping Yuan1
1 Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
2 School of Life Sciences, University of Nottingham, Medical School, Queen’s Medical Centre, Nottingham, NG7 2UH, United Kingdom.
* Present address: University Hospital Jena, Institute for Diagnostic and Interventional Radiology, Experimental Radiology, Erlanger Allee 101, 07747 Jena, Germany
Dr. Juping Yuan, email:
Keywords: MCAK/Plk1/protein stability/chromosome alignment/spindle assembly
Received: February 19, 2014 Accepted: March 24, 2014 Published: March 24, 2014
Proper bi-orientation of chromosomes is critical for the accurate segregation of chromosomes in mitosis. A key regulator of this process is MCAK, the mitotic centromere-associated kinesin. During mitosis the activity and localization of MCAK are regulated by mitotic key kinases including Plk1 and Aurora B. We show here that S621 in the MCAK’s C-terminal domain is the major phosphorylation site for Plk1. This phosphorylation regulates MCAK’s stability and facilitates its recognition by the ubiquitin/proteasome dependent APC/CCdc20 pathway leading to its D-box dependent degradation in mitosis. While phosphorylation of S621 does not directly affect its microtubule depolymerising activity, loss of Plk1 phosphorylation on S621 indirectly enhances its depolymerization activity in vivo by stabilizing MCAK, leading to an increased level of protein. Interfering with phosphorylation at S621 causes spindle formation defects and chromosome misalignments. Therefore, this study suggests a new mechanism by which Plk1 regulates MCAK: by regulating its degradation and hence controlling its turnover in mitosis.
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