Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation

EMBO J. 2013 Jun 12;32(12):1761-77. doi: 10.1038/emboj.2013.109. Epub 2013 May 17.

Abstract

Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase-promoting complex/cyclosome-inhibitory complexes to levels that ensure long-term SAC activity. We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinases
  • Cdc20 Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Kinetochores / metabolism*
  • Phosphorylation / physiology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*

Substances

  • BubR1 protein, Drosophila
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Drosophila Proteins
  • fzy protein, Drosophila
  • polo protein, Drosophila
  • Aurora Kinases
  • Mps1 protein, Drosophila
  • Protein-Serine-Threonine Kinases