Functional and spatial regulation of mitotic centromere-associated kinesin by cyclin-dependent kinase 1.
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.
Sanhaji
Mourad
M
Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Friel
Claire Therese
CT
Kreis
Nina-Naomi
NN
Krämer
Andrea
A
Martin
Claudia
C
Howard
Jonathon
J
Strebhardt
Klaus
K
Yuan
Juping
J
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*
D045163:Antibodies, Phospho-Specific; D056744:Cyclin B1; C091489:KIF2C protein, human; D016203:CDC2 Protein Kinase; D016547:Kinesins