title: Cdk1 orders mitotic events through coordination of a chromosome-associated phosphatase switch.
abstract: RepoMan is a scaffold for signalling by mitotic phosphatases at the chromosomes. During (pro)metaphase, RepoMan-associated protein phosphatases PP1 and PP2A-B56 regulate the chromosome targeting of Aurora-B kinase and RepoMan, respectively. Here we show that this task division is critically dependent on the phosphorylation of RepoMan by protein kinase Cyclin-dependent kinase 1 (Cdk1), which reduces the binding of PP1 but facilitates the recruitment of PP2A-B56. The inactivation of Cdk1 in early anaphase reverses this phosphatase switch, resulting in the accumulation of PP1-RepoMan to a level that is sufficient to catalyse its own chromosome targeting in a PP2A-independent and irreversible manner. Bulk-targeted PP1-RepoMan also inactivates Aurora B and initiates nuclear-envelope reassembly through dephosphorylation-mediated recruitment of Importin β. Bypassing the Cdk1 regulation of PP1-RepoMan causes the premature dephosphorylation of its mitotic-exit substrates in prometaphase. Hence, the regulation of RepoMan-associated phosphatases by Cdk1 is essential for the timely dephosphorylation of their mitotic substrates.
authors.affiliation: Laboratory of Biosignaling &Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, O&N1, Herestraat 49, Box 901, Leuven B-3000, Belgium.
authors.forename: Junbin
authors.identifier: http://orcid.org/0000-0001-6145-045X
authors.initials: J
authors.lastname: Qian
authors.affiliation: Laboratory of Biosignaling &Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, O&N1, Herestraat 49, Box 901, Leuven B-3000, Belgium.
authors.forename: Monique
authors.initials: M
authors.lastname: Beullens
authors.affiliation: Laboratory of Biosignaling &Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, O&N1, Herestraat 49, Box 901, Leuven B-3000, Belgium.|Department of Biochemistry and Molecular Biology, Guizhou Medical University, Guiyang, Guizhou 550025, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Laboratory of Biosignaling &Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, O&N1, Herestraat 49, Box 901, Leuven B-3000, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: De Munter
authors.affiliation: Laboratory of Biosignaling &Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, O&N1, Herestraat 49, Box 901, Leuven B-3000, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Lesage
authors.affiliation: Laboratory of Biosignaling &Therapeutics, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, O&N1, Herestraat 49, Box 901, Leuven B-3000, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bollen
mesh_terms: D000705:Anaphase; D064107:Aurora Kinase B / Q000378:metabolism*; D016203:CDC2 Protein Kinase; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002875:Chromosomes / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008938:Mitosis / Q000235:genetics*; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases; D049468:Prometaphase; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*
chemical_list: C509224:CDCA2 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D028961:beta Karyopherins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D010744:Phosphoric Monoester Hydrolases