title: PP1/Repo-man dephosphorylates mitotic histone H3 at T3 and regulates chromosomal aurora B targeting.
abstract: The transient mitotic histone H3 phosphorylation by various protein kinases regulates chromosome condensation and segregation, but the counteracting phosphatases have been poorly characterized [1-8]. We show here that PP1γ is the major histone H3 phosphatase acting on the mitotically phosphorylated (ph) residues H3T3ph, H3S10ph, H3T11ph, and H3S28ph. In addition, we identify Repo-Man, a chromosome-bound interactor of PP1γ [9], as a selective regulator of H3T3ph and H3T11ph dephosphorylation. Repo-Man promotes H3T11ph dephosphorylation by an indirect mechanism but directly and specifically targets H3T3ph for dephosphorylation by associated PP1γ. The PP1γ/Repo-Man complex opposes the protein kinase Haspin-mediated spreading of H3T3ph to the chromosome arms until metaphase and catalyzes the net dephosphorylation of H3T3ph at the end of mitosis. Consistent with these findings, Repo-Man modulates in a PP1-dependent manner the H3T3ph-regulated chromosomal targeting of Aurora kinase B and its substrate MCAK. Our study defines a novel mechanism by which PP1 counteracts Aurora B.
authors.affiliation: Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, University of Leuven, B-3000 Leuven, Belgium.
authors.forename: Junbin
authors.initials: J
authors.lastname: Qian
authors.forename: Bart
authors.initials: B
authors.lastname: Lesage
authors.forename: Monique
authors.initials: M
authors.lastname: Beullens
authors.forename: Aleyde
authors.initials: A
authors.lastname: Van Eynde
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bollen
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D020090:Chromosome Segregation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D016547:Kinesins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*
chemical_list: C509224:CDCA2 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D006657:Histones; C091489:KIF2C protein, human; D009687:Nuclear Proteins; D017476:Receptors, Neuropeptide Y; C109491:neuropeptide Y4 receptor; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins