The spindle and kinetochore-associated (Ska) protein complex is required for accurate chromosome segregation during mitosis [1-6] and consists of two copies each of Ska1, Ska2, and Ska3 proteins [4, 7]. The Ska complex contains multiple microtubule-binding elements and promotes kinetochore-microtubule attachment [8-11]. The Ska1 C-terminal domain (CTD) recruits protein phosphatase 1 (PP1) to kinetochores to promote timely anaphase onset . The Ska complex regulates, and is regulated by, Aurora B . Aurora B phosphorylates both Ska1 and Ska3 to inhibit the kinetochore localization of the Ska complex . Despite its multitude of functions at kinetochores, how the Ska complex itself is recruited to kinetochores is unclear. It is unknown whether any mitotic kinases positively regulate the localization of the Ska complex to kinetochores. Here, we show that Cdk1 phosphorylates Ska3 to promote its direct binding to the Ndc80 complex (Ndc80C), a core outer kinetochore component. We also show that this phosphorylation occurs specifically during mitosis and is required for the kinetochore localization of the Ska complex. Ska3 mutants deficient in Cdk1 phosphorylation are defective in kinetochore localization but retain microtubule localization. These mutants support chromosome alignment but delay anaphase onset. We propose that Ska3 phosphorylated by Cdk1 in mitosis binds to Ndc80C and recruits the Ska complex to kinetochores where Ska1 can bind both PP1 and microtubules to promote anaphase onset.
Pubmed ID: 28479321 RIS Download
Mesh terms: Aurora Kinase B | CDC2 Protein Kinase | Chromosomal Proteins, Non-Histone | Chromosome Segregation | HeLa Cells | Humans | Kinetochores | Microtubule-Associated Proteins | Microtubules | Mitosis | Nuclear Proteins | Phosphorylation
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