Mutual regulation between the spindle checkpoint and APC/C

Semin Cell Dev Biol. 2011 Aug;22(6):551-8. doi: 10.1016/j.semcdb.2011.03.008. Epub 2011 Mar 23.

Abstract

Accurate chromosome segregation during mitosis is critical for maintaining genomic stability. The spindle checkpoint is a cellular surveillance system that ensures the fidelity of chromosome segregation. In response to sister chromatids not properly captured by spindle microtubules, the spindle checkpoint interferes with the functions of Cdc20, the mitotic activator of the anaphase-promoting complex or cyclosome (APC/C), thereby blocking APC/C-mediated degradation of securin and cyclin B to delay anaphase onset. This review summarizes the recent progress on the mechanisms by which checkpoint proteins inhibit APC/C, the conformational and enzymatic activation of checkpoint proteins, and the emerging roles of APC/C-dependent ubiquitination in checkpoint inactivation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatids
  • Chromosome Segregation*
  • Chromosomes / genetics
  • Chromosomes / metabolism*
  • Dyneins / genetics
  • Dyneins / metabolism
  • Gene Expression Regulation / physiology*
  • Genomic Instability
  • Humans
  • M Phase Cell Cycle Checkpoints / physiology*
  • Mice
  • Microtubules
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / metabolism*
  • Ubiquitination

Substances

  • Cell Cycle Proteins
  • MXD3 protein, human
  • Repressor Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases
  • Dyneins