State of the APC/C: organization, function, and structure

Crit Rev Biochem Mol Biol. 2011 Apr;46(2):118-36. doi: 10.3109/10409238.2010.541420. Epub 2011 Jan 24.


The ubiquitin-proteasome protein degradation system is involved in many essential cellular processes including cell cycle regulation, cell differentiation, and the unfolded protein response. The anaphase-promoting complex/cyclosome (APC/C), an evolutionarily conserved E3 ubiquitin ligase, was discovered 15 years ago because of its pivotal role in cyclin degradation and mitotic progression. Since then, we have learned that the APC/C is a very large, complex E3 ligase composed of 13 subunits, yielding a molecular machine of approximately 1 MDa. The intricate regulation of the APC/C is mediated by the Cdc20 family of activators, pseudosubstrate inhibitors, protein kinases and phosphatases and the spindle assembly checkpoint. The large size, complexity, and dynamic nature of the APC/C represent significant obstacles toward high-resolution structural techniques; however, over the last decade, there have been a number of lower resolution APC/C structures determined using single particle electron microscopy. These structures, when combined with data generated from numerous genetic and biochemical studies, have begun to shed light on how APC/C activity is regulated. Here, we discuss the most recent developments in the APC/C field concerning structure, substrate recognition, and catalysis.

Publication types

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

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Catalysis
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism
  • Cell Nucleus / metabolism
  • Humans
  • Meiosis
  • Microscopy, Electron
  • Mitosis
  • Models, Biological
  • Spindle Apparatus / metabolism
  • Ubiquitin-Protein Ligase Complexes / chemistry*
  • Ubiquitin-Protein Ligase Complexes / metabolism*
  • Ubiquitin-Protein Ligases / metabolism


  • Cell Cycle Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases