title: Aurora B phosphorylates multiple sites on mitotic centromere-associated kinesin to spatially and temporally regulate its function.
abstract: Chromosome congression and segregation require the proper attachment of microtubules to the two sister kinetochores. Disruption of either Aurora B kinase or the Kinesin-13 mitotic centromere-associated kinesin (MCAK) increases chromosome misalignment and missegregation due to improper kinetochore-microtubule attachments. MCAK localization and activity are regulated by Aurora B, but how Aurora B phosphorylation of MCAK affects spindle assembly is unclear. Here, we show that the binding of MCAK to chromosome arms is also regulated by Aurora B and that Aurora B-dependent chromosome arm and centromere localization is regulated by distinct two-site phosphoregulatory mechanisms. MCAK association with chromosome arms is promoted by phosphorylation of T95 on MCAK, whereas phosphorylation of S196 on MCAK promotes dissociation from the arms. Although targeting of MCAK to centromeres requires phosphorylation of S110 on MCAK, dephosphorylation of T95 on MCAK increases the binding of MCAK to centromeres. Our study reveals a new role for Aurora B, which is to prevent excess MCAK binding to chromatin to facilitate chromatin-nucleated spindle assembly. Our study also shows that the interplay between multiple phosphorylation sites of MCAK may be critical to temporally and spatially control MCAK function.
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Weijie
authors.initials: W
authors.lastname: Lan
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Ems-McClung
authors.forename: P Todd
authors.initials: PT
authors.lastname: Stukenberg
authors.forename: Claire E
authors.initials: CE
authors.lastname: Walczak
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D064127:Aurora Kinases; D002453:Cell Cycle; D002457:Cell Extracts; D002503:Centromere / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D010063:Ovum; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*
chemical_list: D002457:Cell Extracts; D002843:Chromatin; D050505:Mutant Proteins; D029867:Xenopus Proteins; C509242:mitotic centromere-associated kinesin, Xenopus; D010769:Phosphothreonine; D010768:Phosphoserine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins