title: Aurora B controls kinetochore-microtubule attachments by inhibiting Ska complex-KMN network interaction.
abstract: The KMN network (named according to the acronym for KNL1, Mis12, and Ndc80) and the more recently identified Ska complex (Ska1-3) have been shown to mediate kinetochore (KT)-microtubule (MT) attachments. How these two complexes cooperate to achieve stable end-on attachments remains unknown. In this paper, we show that Aurora B negatively regulates the localization of the Ska complex to KTs and that recruitment of the Ska complex to KTs depends on the KMN network. We identified interactions between members of the KMN and Ska complexes and demonstrated that these interactions are regulated by Aurora B. Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments.
authors.affiliation: Growth and Development, Biozentrum, University of Basel, 4056 Basel, Switzerland.
authors.forename: Ying Wai
authors.initials: YW
authors.lastname: Chan
authors.forename: A Arockia
authors.initials: AA
authors.lastname: Jeyaprakash
authors.forename: Erich A
authors.initials: EA
authors.lastname: Nigg
authors.forename: Anna
authors.initials: A
authors.lastname: Santamaria
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; C532764:DSN1 protein, human; C472643:Knl1 protein, human; D008869:Microtubule-Associated Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C516427:SKA1 protein, human; C516428:SKA2 protein, human; C541140:Ska3 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases