Deregulation of Anaphase-promoting Complex/cyclosome-dependent Proteolysis in Cancer

Abnormal regulation of the cell cycle is essential for oncogenic transformation and tumor progression. The cell cycle is driven by the activity of the Cyclin/Cyclin/dependent kinase (Cdk) complex. Recently, the protein level of various cell cycle regulators including Cyclins and Cdk inhibitors was found to be regulated by the ubiquitin-proteasome pathway. In particular, SCF (Skp1-Cullin-F-box) and the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex play an important role in the ubiquitin-mediated proteolysis of cell cycle regulators. It has recently been revealed that the overexpression of oncogenic cell cycle regulators and reduced expression of tumor suppressive cell cycle regulators are caused by the abnormal regulation of ubiquitin-mediated proteolysis in cancer. In this review, we introduce the deregulation of APC/C ubiquitin ligase complex-dependent proteolysis in cancer.