Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation

• Main Authors: Amanda Meppelink, Lilian Kabeche, Martijn J.M. Vromans, Duane A. Compton, Susanne M.A. Lens
• Format: Article
• Language: English
• Published: Elsevier 2015-04-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124715003435

Correction of faulty kinetochore-microtubule attachments is essential for faithful chromosome segregation and dictated by the opposing activities of Aurora B kinase and PP1 and PP2A phosphatases. How kinase and phosphatase activities are appropriately balanced is less clear. Here, we show that a centromeric pool of PP2A-B56 counteracts Aurora B T-loop phosphorylation and is recruited to centromeres through Shugoshin-1 (Sgo1). In non-transformed RPE-1 cells, Aurora B, Sgo1, and PP2A-B56 are enriched on centromeres and levels diminish as chromosomes establish bi-oriented attachments. Elevating Sgo1 levels at centromeres recruits excess PP2A-B56, and this counteracts Aurora B kinase activity, undermining efficient correction of kinetochore-microtubule attachment errors. Conversely, Sgo1-depleted cells display reduced centromeric localization of Aurora B, whereas the remaining kinase is hyperactive due to concomitant reduction of centromeric PP2A-B56. Our data suggest that Sgo1 can tune the stability of kinetochore-microtubule attachments through recruitment of PP2A-B56 that balances Aurora B activity at the centromere.