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

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.