title: Opposing Activities of Aurora B Kinase and B56-PP2A Phosphatase on MKlp2 Determine Abscission Timing.
abstract: After cleavage furrow ingression during cytokinesis, nascent daughter cells remain connected by an intercellular bridge (ICB) and the midbody [1, 2]. The midbody becomes an assembly platform for ESCRT complexes that split apart the plasma membrane (PM) anchored to the ICB and complete abscission, which is the final step of cell division [3-5]. Aurora B governs abscission by regulating its timing as a checkpoint [6-10]. However, the underlying mechanisms for this process remain unknown. Here, we reveal the mechanism controlling abscission through integration of Aurora B kinase and B56-bound PP2A phosphatase activities on the kinesin motor protein MKlp2. We identify MKlp2 as an essential protein for promoting abscission, which may regulate tethering and stabilizing of the PM to the microtubule cytoskeleton at the ICB through its previously uncharacterized lipid association motif (LAM). MKlp2 recruits Aurora B to the ICB [11-15]. In turn, Aurora B phosphorylation of MKlp2 S878 in the LAM is a key inhibitory signal for abscission. Conversely, B56-PP2A promotes abscission by opposing Aurora B phosphorylation of MKlp2 S878. Strikingly, a phospho-resistant MKlp2 S878A mutant overcomes Aurora-B-mediated abscission blockade. Thus, abscission is determined by the balance of Aurora B and B56-PP2A activities on MKlp2 S878 within the LAM. Together, these findings establish a key mechanism for Aurora B regulation of abscission in mammalian cells.
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Suet Yin Sarah
authors.initials: SYS
authors.lastname: Fung
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Pei-Ju
authors.initials: PJ
authors.lastname: Liao
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Wong
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Electronic address: sanghyun.lee@duke-nus.edu.sg.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Lee
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism*; D002455:Cell Division; D048749:Cytokinesis; D003599:Cytoskeleton / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C410089:KIF20A protein, human; C525690:PPP2R5A protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D054648:Protein Phosphatase 2; D016547:Kinesins
keywords: Aurora B; ESCRT; MKlp2; PP2A; abscission; plasma membrane