KIF4A and PP2A-B56 form a spatially restricted feedback loop opposing Aurora B at the anaphase central spindle.

ABSTRACT: The mitotic kinase Aurora B is concentrated at the anaphase central spindle by the kinesin MKlp2 during mitotic exit and cytokinesis. This pool of Aurora B phosphorylates substrates including the kinesin KIF4A to regulate central spindle length. In this paper, we identify a counteracting system in which PP2A-B56? and -?, but not PP2A-B56?, -?, and -?, are maintained at the central spindle by KIF4A. Biochemical assays show that PP2A-B56? can dephosphorylate the T799 Aurora B site on KIF4A and thereby counteract the Aurora B- and microtubule-stimulated ATPase activity of KIF4A. In agreement with these observations, combined silencing of PP2A-B56? and -? resulted in increased phosphorylation of KIF4A T799 and decreased central spindle growth in anaphase B. Furthermore, reduced turnover of regulatory phosphorylation on another Aurora B substrate MKlp1 was observed, suggesting that PP2A-B56? and -? play a general role opposing Aurora B at the central spindle. KIF4A and PP2A-B56? and -? therefore create a spatially restricted negative feedback loop counteracting Aurora B in anaphase.

SUBMITTER: Bastos RN 

PROVIDER: S-EPMC4274259 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature