Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis

  • 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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Author:Mourad Sanhaji, Andreas Ritter, Hannah R. Belsham, Claire T. Friel, Susanne Roth, Frank LouwenGND, Juping Yuan
URN:urn:nbn:de:hebis:30:3-335622
DOI:https://doi.org/10.18632/oncotarget.1861
ISSN:1949-2553
Parent Title (English):Oncotarget
Publisher:Impact Journals LLC
Place of publication:[S.l.]
Document Type:Article
Language:English
Date of Publication (online):2014/03/24
Date of first Publication:2014/03/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/05/30
Tag:MCAK; Plk1; chromosome alignment; protein stability; spindle assembly
Volume:10
Issue:5
Page Number:15
First Page:3130
Last Page:3144
Note:
Licensed under a Creative Commons Attribution 3.0 License. http://creativecommons.org/licenses/by/3.0/
HeBIS-PPN:399892834
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0