Mps1 promotes rapid centromere accumulation of Aurora B

EMBO Rep. 2012 Sep;13(9):847-54. doi: 10.1038/embor.2012.93. Epub 2012 Jun 26.

Abstract

Aurora B localization to mitotic centromeres, which is required for proper chromosome alignment during mitosis, relies on Haspin-dependent histone H3 phosphorylation and on Bub1-dependent histone H2A phosphorylation--which interacts with Borealin through a Shugoshin (Sgo) intermediate. We demonstrate that Mps1 stimulates the latter recruitment axis. Mps1 activity enhances H2A-T120ph and is critical for Sgo1 recruitment to centromeres, thereby promoting Aurora B centromere recruitment in early mitosis. Importantly, chromosome biorientation defects caused by Mps1 inhibition are improved by restoring Aurora B centromere recruitment. As Mps1 kinetochore localization reciprocally depends on Aurora B, we propose that this Aurora B-Mps1 recruitment circuitry cooperates with the Aurora B-Haspin feedback loop to ensure rapid centromere accumulation of Aurora B at the onset of mitosis.

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins / metabolism*
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kinetochores / enzymology*
  • Mitosis
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • Cell Cycle Proteins
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • SGO1 protein, human
  • Protein-Tyrosine Kinases
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • HASPIN protein, human
  • Protein Serine-Threonine Kinases
  • TTK protein, human