Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction

EMBO J. 2011 Apr 20;30(8):1508-19. doi: 10.1038/emboj.2011.70. Epub 2011 Mar 15.

Abstract

Fidelity of chromosome segregation is ensured by a tension-dependent error correction system that prevents stabilization of incorrect chromosome-microtubule attachments. Unattached or incorrectly attached chromosomes also activate the spindle assembly checkpoint, thus delaying mitotic exit until all chromosomes are bioriented. The Aurora B kinase is widely recognized as a component of error correction. Conversely, its role in the checkpoint is controversial. Here, we report an analysis of the role of Aurora B in the spindle checkpoint under conditions believed to uncouple the effects of Aurora B inhibition on the checkpoint from those on error correction. Partial inhibition of several checkpoint and kinetochore components, including Mps1 and Ndc80, strongly synergizes with inhibition of Aurora B activity and dramatically affects the ability of cells to arrest in mitosis in the presence of spindle poisons. Thus, Aurora B might contribute to spindle checkpoint signalling independently of error correction. Our results support a model in which Aurora B is at the apex of a signalling pyramid whose sensory apparatus promotes the concomitant activation of error correction and checkpoint signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B
  • Aurora Kinases
  • Chromosome Segregation
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Kinetochores / physiology*
  • Mitosis / physiology*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / genetics
  • Signal Transduction / drug effects*
  • Spindle Apparatus / physiology*

Substances

  • Enzyme Inhibitors
  • RNA, Small Interfering
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases