Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment

Cell. 2008 Jan 25;132(2):233-46. doi: 10.1016/j.cell.2007.11.046.

Abstract

Maintenance of chromosomal stability relies on coordination between various processes that are critical for proper chromosome segregation in mitosis. Here we show that monopolar spindle 1 (Mps1) kinase, which is essential for the mitotic checkpoint, also controls correction of improper chromosome attachments. We report that Borealin/DasraB, a member of the complex that regulates the Aurora B kinase, is directly phosphorylated by Mps1 on residues that are crucial for Aurora B activity and chromosome alignment. As a result, cells lacking Mps1 kinase activity fail to efficiently align chromosomes due to impaired Aurora B function at centromeres, leaving improper attachments uncorrected. Strikingly, Borealin/DasraB bearing phosphomimetic mutations restores Aurora B activity and alignment in Mps1-depleted cells. Mps1 thus coordinates attachment error correction and checkpoint signaling, two crucial responses to unproductive chromosome attachments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology*
  • Cell Line, Tumor
  • Chromosomes, Human / metabolism*
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • Microtubules / metabolism
  • Mutation
  • Phosphorylation
  • Plasmids
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / physiology*
  • Protein-Tyrosine Kinases
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / metabolism
  • Spindle Apparatus / metabolism
  • Transfection

Substances

  • CDCA8 protein, human
  • Cell Cycle Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • Protein-Tyrosine Kinases
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • TTK protein, human