title: 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-B56γ and -ε, but not PP2A-B56α, -β, and -δ, are maintained at the central spindle by KIF4A. Biochemical assays show that PP2A-B56γ 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-B56γ and -ε 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-B56γ and -ε play a general role opposing Aurora B at the central spindle. KIF4A and PP2A-B56γ and -ε therefore create a spatially restricted negative feedback loop counteracting Aurora B in anaphase.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK.
authors.forename: Ricardo Nunes
authors.initials: RN
authors.lastname: Bastos
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cundell
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK francis.barr@bioch.ox.ac.uk.
authors.forename: Francis A
authors.initials: FA
authors.lastname: Barr
mesh_terms: D000705:Anaphase; D000818:Animals; D064107:Aurora Kinase B / Q000378:metabolism*; D025461:Feedback, Physiological; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D061987:Sf9 Cells; D008941:Spindle Apparatus / Q000201:enzymology; D018411:Spodoptera; D059008:Time-Lapse Imaging
chemical_list: C525692:PPP2R5E protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; C503981:PPP2R5C protein, human; D054648:Protein Phosphatase 2; C484228:KIF4A protein, human; D016547:Kinesins