Targeting the anaphase promoting complex: common pathways for viral infection and cancer therapy

Expert Opin Ther Targets. 2011 Jun;15(6):767-80. doi: 10.1517/14728222.2011.558008. Epub 2011 Mar 5.

Abstract

Introduction: The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase involved in regulation of the cell cycle through ubiquitination-dependent substrate proteolysis. Many viral proteins have been shown to interact with the APC/C, derailing cell cycle progression in order to facilitate their own replication. Induction of G(2)/M arrest by viral APC/C inhibition can lead to apoptotic cell death. Some viral proteins cause cytotoxicity specifically in tumour cells, providing evidence that targeting the APC/C could be exploited to selectively eliminate cancer cells.

Areas covered: In this review, we provide a summary of studies from viral APC/C interactions over the last decade, as well as recent discoveries identifying the APC/C as a promising target in the context of cancer therapy.

Expert opinion: Current therapeutic strategies inducing mitotic arrest rely on activation of the spindle assembly checkpoint (SAC) for their function. Many cancer cells have a weakened SAC and escape apoptosis through mitotic slippage. Recent evidence has demonstrated that targeting the APC/C, particularly the co-activator Cdc20, might be a better alternative. Tumour cells display greater dependency on APC/C function than normal cells and oncogenic transformation can lead to increased mitotic stress, rendering cancer cells more vulnerable to APC/C inhibition.

Publication types

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

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Cycle
  • Drug Delivery Systems*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Ubiquitin-Protein Ligase Complexes / antagonists & inhibitors
  • Ubiquitin-Protein Ligase Complexes / metabolism*
  • Viral Proteins / metabolism
  • Virus Diseases / drug therapy
  • Virus Diseases / virology

Substances

  • Antineoplastic Agents
  • Viral Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome