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

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.

• Authors: Linda Smolders, Jose G Teodoro
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 15 Issue 6 Pg. 767-80 (Jun 2011) ISSN: 1744-7631 [Electronic] England
• PMID: 21375465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

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

Topics

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