Insights into the anaphase-promoting complex: a molecular machine that regulates mitosis

Curr Opin Struct Biol. 2014 Dec;29:1-9. doi: 10.1016/j.sbi.2014.08.003. Epub 2014 Aug 24.

Abstract

The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric complex that functions as a RING domain E3 ubiquitin ligase to regulate ordered transitions through the cell cycle. It does so by controlling the ubiquitin-mediated proteolysis of cell cycle proteins, notably cyclins and securins, whose degradation triggers sister chromatid disjunction and mitotic exit. Regulation of APC/C activity and modulation of its substrate specificity are subject to intricate cell cycle checkpoints and control mechanisms involving the switching of substrate-specifying cofactors, association of regulatory protein complexes and post-translational modifications. This review discusses the recent progress towards understanding the overall architecture of the APC/C, the molecular basis for degron recognition and ubiquitin chain synthesis, and how these activities are regulated.

Publication types

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

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Cell Cycle Proteins / metabolism
  • F-Box Proteins / metabolism
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Mitosis*
  • Multiprotein Complexes / metabolism*
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Proteolysis
  • Substrate Specificity
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Cell Cycle Proteins
  • F-Box Proteins
  • FBXO5 protein, human
  • Multiprotein Complexes
  • Ubiquitin
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases