title: The activity regulation of the mitotic centromere-associated kinesin by Polo-like kinase 1.
abstract: The mitotic centromere-associated kinesin (MCAK), a potent microtubule depolymerase, is involved in regulating microtubule dynamics. The activity and subcellular localization of MCAK are tightly regulated by key mitotic kinases, such as Polo-like kinase 1 (Plk1) by phosphorylating multiple residues in MCAK. Since Plk1 phosphorylates very often different residues of substrates at different stages, we have dissected individual phosphorylation of MCAK by Plk1 and characterized its function in more depth. We have recently shown that S621 in MCAK is the major phosphorylation site of Plk1, which is responsible for regulating MCAK's degradation by promoting the association of MCAK with APC/CCdc20. In the present study, we have addressed another two residues phosphorylated by Plk1, namely S632/S633 in the C-terminus of MCAK. Our data suggest that Plk1 phosphorylates S632/S633 and regulates its catalytic activity in mitosis. This phosphorylation is required for proper spindle assembly during early phases of mitosis. The subsequent dephosphorylation of S632/S633 might be necessary to timely align the chromosomes onto the metaphase plate. Therefore, our studies suggest new mechanisms by which Plk1 regulates MCAK: the degradation of MCAK is controlled by Plk1 phosphorylation on S621, whereas its activity is modulated by Plk1 phosphorylation on S632/S633 in mitosis.
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, 60590 Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritter
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, 60590 Frankfurt, Germany.|Present address: University Hospital Jena, Institute for Diagnostic and Interventional Radiology, Experimental Radiology, 07747 Jena, Germany.
authors.forename: Mourad
authors.initials: M
authors.lastname: Sanhaji
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, 60590 Frankfurt, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Steinhäuser
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, 60590 Frankfurt, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Roth
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, 60590 Frankfurt, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Louwen
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe-University, 60590 Frankfurt, Germany.
authors.forename: Juping
authors.initials: J
authors.lastname: Yuan
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002503:Centromere / Q000201:enzymology*; D020090:Chromosome Segregation; D004789:Enzyme Activation; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008677:Metaphase; D008870:Microtubules / Q000201:enzymology; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D012694:Serine; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000201:enzymology; D013997:Time Factors; D014162:Transfection; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012694:Serine; D000097869:Polo-Like Kinase 1; C091489:KIF2C protein, human
keywords: MCAK; Plk1; chromosome alignment; phosphorylation; spindle assembly