To cell cycle, swing the APC/C

Biochim Biophys Acta. 2008 Sep;1786(1):49-59. doi: 10.1016/j.bbcan.2008.05.002. Epub 2008 May 21.

Abstract

For successful mitosis, Cyclin B1 and Securin must be degraded efficiently before anaphase. Destruction of these mitotic regulators by the 26S proteasome is the result of their poly-ubiquitination by a multi-subunit E3 ligase: the Anaphase-Promoting Complex or Cyclosome (APC/C). Clearly, the APC/C is not just important for mitosis. Destruction of APC/C substrates such as Cdc20, Plk1, Aurora A and Skp2 directs events in G1. Strikingly, the APC/C needs to stay active even in quiescent cells to keep them out of the cell cycle and forms an intriguing link with pRb. An inactive APC/C stabilizes Geminin, Cyclin A and Cyclin B1, thereby securing completion of DNA synthesis and progression through G2-phase. In prometaphase the APC/C becomes active again, but is controlled by the spindle assembly checkpoint. Here we discuss how the APC/C is either held in check or released. We argue that shedding more light on the APC/C is also important to understand cancer and could help the design of treatment.

Publication types

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

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Antigens, CD
  • CDC2 Protein Kinase / physiology
  • Cadherins / physiology
  • Cdc20 Proteins
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / physiology
  • Cyclin B / metabolism*
  • DNA Damage
  • G2 Phase / physiology
  • Humans
  • Models, Molecular
  • Neoplasm Proteins / metabolism*
  • Neoplasms / etiology
  • S Phase / physiology
  • Securin
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / physiology
  • Ubiquitin-Protein Ligase Complexes / physiology*
  • Ubiquitin-Protein Ligases / physiology
  • Ubiquitination

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Cyclin B
  • Neoplasm Proteins
  • Securin
  • pituitary tumor-transforming protein 1, human
  • CDC20 protein, human
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • CDC2 Protein Kinase