Cdk1 orders mitotic events through coordination of a chromosome-associated phosphatase switch
Junbin Qian,
Monique Beullens,
Jin Huang,
Sofie De Munter,
Bart Lesage and
Mathieu Bollen ()
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Junbin Qian: Laboratory of Biosignaling & Therapeutics, University of Leuven, Campus Gasthuisberg, O&N1
Monique Beullens: Laboratory of Biosignaling & Therapeutics, University of Leuven, Campus Gasthuisberg, O&N1
Jin Huang: Laboratory of Biosignaling & Therapeutics, University of Leuven, Campus Gasthuisberg, O&N1
Sofie De Munter: Laboratory of Biosignaling & Therapeutics, University of Leuven, Campus Gasthuisberg, O&N1
Bart Lesage: Laboratory of Biosignaling & Therapeutics, University of Leuven, Campus Gasthuisberg, O&N1
Mathieu Bollen: Laboratory of Biosignaling & Therapeutics, University of Leuven, Campus Gasthuisberg, O&N1
Nature Communications, 2015, vol. 6, issue 1, 1-13
Abstract:
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.
Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10215
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DOI: 10.1038/ncomms10215
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