title: Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis.
abstract: 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/C(Cdc20) 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.
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
authors.forename: Mourad
authors.initials: M
authors.lastname: Sanhaji
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritter
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Belsham
authors.forename: Claire T
authors.initials: CT
authors.lastname: Friel
authors.forename: Susanne
authors.initials: S
authors.lastname: Roth
authors.forename: Frank
authors.initials: F
authors.lastname: Louwen
authors.forename: Juping
authors.initials: J
authors.lastname: Yuan
mesh_terms: D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D016547:Kinesins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055550:Protein Stability; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C091489:KIF2C protein, human