A molecular explanation for PP2A-B56 isoform specificity during mitosis
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 shared between B56 isoforms which 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. The molecular basis for this differential localisation can be mapped to a small C-terminal region in B56 that regulates these key interactions and defines whether PP2A-B56 complexes bind to either the centromere or kinetochore. Together, this study describes how different PP2A-B56 complexes utilise isoform-specific interactions to control distinct processes during mitosis.