SCF和APC/C的结构及功能

The Structure and Function of SCF and APC/C

细胞周期蛋白依赖性蛋白激酶(cyclin dependent kinases,CDKs)是细胞周期进行的推动力,泛素-蛋白酶体途径(ubiquitin-proteasome pathway,UPP)通过对细胞周期蛋白(cyclin)和CDK抑制物(CDK inhibitors,CKIs)的蛋白质水解作用来实现对CDKs活性的调控。SCF(Skp1-Cul1-F-box protein)和APC/C(anaphase-promoting complex/cyclosome)这两个泛素连接酶复合物参与了很多细胞周期调节因子的泛素化作用。它们参与的蛋白质降解系统的功能失调可能导致细胞增殖紊乱、基因组不稳定和肿瘤的发生。现对这两个泛素连接酶复合物的结构以及它们在细胞周期调控和肿瘤发生机制中的作用进行综述。

The cyclin-dependent kinases （CDKs） is a driving force of the cell cycle, and the activities of CDKs are controlled by the ubiquitin-proteasome pathway （UPP） through proteolysis of key regulators such as cyclins and CDK inhibitors. Two ubiquitin ligases, the Skpl-Cull-F-box protein （SCF） complex and the anaphasepromoting complex/cyclosome （APC/C）, are responsible for the specific ubiquitylation of many regulators in cell cycle. Deregulation of the proteolytic system might result in uncontrolled proliferation, genomic instability and cancer. In this review, the structures of these two ubiquitin ligases and their functions in mechanisms of cell cycle control and cancer were summarized.