Spindle checkpoint silencing: PP1 tips the balance

Curr Biol. 2011 Nov 8;21(21):R898-903. doi: 10.1016/j.cub.2011.08.063.

Abstract

The spindle checkpoint is a mitotic surveillance mechanism that delays anaphase until all sister chromatids are correctly attached to microtubules from opposite poles. Recent studies reveal that protein kinase Aurora B is a key regulator of spindle checkpoint activation whereas protein phosphatase PP1 antagonizes Aurora B and induces checkpoint silencing. Chromosome biorientation stretches the kinetochores and spatially separates centromeric Aurora B from its kinetochore substrates, comprising several PP1-interacting proteins (PIPs). The ensuing dephosphorylation of these PIPs creates docking sites for the bulk recruitment of PP1 to the kinetochores. We propose that this tension-induced targeting of PP1 triggers checkpoint silencing by the dephosphorylation of kinetochore and checkpoint components, including Aurora B substrates. In addition, PP1 also directly inactivates a kinetochore-associated pool of Aurora B and silences checkpoint signaling by opposing the centromeric targeting of Aurora B.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaphase
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Cycle Checkpoints*
  • Chromatids / metabolism
  • Chromosome Segregation
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Humans
  • Kinetochores / metabolism
  • Microtubules / metabolism
  • Phosphorylation
  • Protein Phosphatase 1 / genetics
  • Protein Phosphatase 1 / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Yeasts / cytology
  • Yeasts / enzymology
  • Yeasts / metabolism

Substances

  • Fungal Proteins
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Protein Phosphatase 1