ユビキチン分解による細胞周期制御とその破綻がもたらす癌化

In the process of carcinogenesis, abnormal regulation of cell cycle regulators is essential. Cell cycle is driven by the activity of Cyclin/Cyclin-dependent kinase (Cdk) complex. The activity of Cyclin/Cdk1 is regulated by the ubiquitin-proteasome pathway via controlling protein level of Cyclins. In addition to Cyclins, the protein level of various cell cycle regulators is strictly and precisely regulated by the ubiquitin-proteasome pathway. In particular, SCF (Skp1-Cullin-F-box) and anaphasepromoting complex/cyclosome (APC/C) ubiquitin ligase complex are involved in ubiquitylation of cell cycle regulators. It recently has been shown that overexpression of oncogenic cell cycle regulators and reduced expression of tumor suppressive cell cycle regulators are caused by abnormal regulation of ubiquitin-mediated proteolysis in cancer. In this review, we introduce abnormal regulation of cell cycle regulators in cancer.