PP1/Repo-man dephosphorylates mitotic histone H3 at T3 and regulates chromosomal aurora B targeting

Curr Biol. 2011 May 10;21(9):766-73. doi: 10.1016/j.cub.2011.03.047. Epub 2011 Apr 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Chromosome Segregation / physiology*
  • Gene Knockdown Techniques
  • Histones / metabolism*
  • Humans
  • Image Processing, Computer-Assisted
  • Immunoblotting
  • Kinesin / metabolism
  • Microscopy, Fluorescence
  • Mitosis / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / metabolism*

Substances

  • CDCA2 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Histones
  • KIF2C protein, human
  • Nuclear Proteins
  • Receptors, Neuropeptide Y
  • neuropeptide Y4 receptor
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Kinesin