title: Functional and spatial regulation of mitotic centromere-associated kinesin by cyclin-dependent kinase 1.
abstract: Mitotic centromere-associated kinesin (MCAK) plays an essential role in spindle formation and in correction of improper microtubule-kinetochore attachments. The localization and activity of MCAK at the centromere/kinetochore are controlled by Aurora B kinase. However, MCAK is also abundant in the cytosol and at centrosomes during mitosis, and its regulatory mechanism at these sites is unknown. We show here that cyclin-dependent kinase 1 (Cdk1) phosphorylates T537 in the core domain of MCAK and attenuates its microtubule-destabilizing activity in vitro and in vivo. Phosphorylation of MCAK by Cdk1 promotes the release of MCAK from centrosomes and is required for proper spindle formation. Interfering with the regulation of MCAK by Cdk1 causes dramatic defects in spindle formation and in chromosome positioning. This is the first study demonstrating that Cdk1 regulates the localization and activity of MCAK in mitosis by directly phosphorylating the catalytic core domain of MCAK.
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Mourad
authors.initials: M
authors.lastname: Sanhaji
authors.forename: Claire Therese
authors.initials: CT
authors.lastname: Friel
authors.forename: Nina-Naomi
authors.initials: NN
authors.lastname: Kreis
authors.forename: Andrea
authors.initials: A
authors.lastname: Krämer
authors.forename: Claudia
authors.initials: C
authors.lastname: Martin
authors.forename: Jonathon
authors.initials: J
authors.lastname: Howard
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebhardt
authors.forename: Juping
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045163:Antibodies, Phospho-Specific / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002503:Centromere / Q000378:metabolism*; D056744:Cyclin B1 / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D045163:Antibodies, Phospho-Specific; D056744:Cyclin B1; C091489:KIF2C protein, human; D016203:CDC2 Protein Kinase; D016547:Kinesins