Abstract
PP2A-B56 is a serine/threonine phosphatase complex that regulates several major mitotic processes, including sister chromatid cohesion, kinetochore-microtubule attachment and the spindle assembly checkpoint. We show here that these key functions are divided between B56 isoforms that localise differentially to either the centromere or kinetochore. The centromeric B56 isoforms rely on a specific interaction with Sgo2, whereas the kinetochore isoforms bind preferentially to BubR1 and other proteins containing an LxxIxE motif. In addition to these selective interactions, Sgo1 also contributes to both localisations by collaborating with BubR1 to maintain B56 isoforms at the kinetochore and helping to anchor the Sgo2/B56 complex at the centromere. A series of chimaeras were used to map the critical region in B56 to a small C-terminal loop that specifies which interactions are favoured and therefore defines where B56 isoforms localise during prometaphase. Together, this study describes how different PP2A-B56 complexes utilise isoform-specific interactions to control distinct processes during mitosis.
