周期蛋白和周期蛋白依赖性激酶及相关激酶抑制剂在细胞周期进程中的调控机制研究进展

Advances of the regulatory mechanism of cyclin, cyclin- dependent kinases and related kinase inhibitors in cell cycle progression

摘要:

在细胞发育过程中，细胞周期起着至关重要的作用。细胞周期进程主要受细胞周期蛋白依赖性激酶(cyclin dependent kinase, CDK)、周期蛋白和内源性CDK抑制剂(cyclin-dependent kinase inhibitors, CKI)调控。其中，CDK是主要的细胞周期调节因子，可与周期蛋白结合形成周期蛋白- CDK复合物，从而使数百种底物磷酸化，调控分裂间期和有丝分裂进程。各类细胞周期蛋白的活性异常，可引起不受控制的癌细胞增殖，导致癌症的发生与发展。因此，了解CDK的活性变化情况、周期蛋白-CDK的组装以及CKI的作用，将有助于了解细胞周期进程中潜在的调控过程，为癌症与疾病的治疗和CKI治疗药物的研发提供基础。本文关注了CDK激活和灭活的关键事件，并总结了周期蛋白-CDK在特定时期及位置的调控过程，以及相关CKI治疗药物在癌症及疾病中的研究进展，最后简单阐述了细胞周期进程研究面临的问题和存在的挑战，以期为后续细胞周期进程的深入研究提供参考和思路。

关键词:周期蛋白依赖性激酶;周期蛋白;周期蛋白依赖性激酶抑制剂;癌症;细胞周期

Abstract:

Cell cycle plays a crucial role in cell development. Cell cycle progression is mainly regulated by cyclin dependent kinase (CDK), cyclin and endogenous CDK inhibitor (CKI). Among these, CDK is the main cell cycle regulator, binding to cyclin to form the cyclin-CDK complex, which phosphorylates hundreds of substrates and regulates interphase and mitotic progression. Abnormal activity of various cell cycle proteins can cause uncontrolled proliferation of cancer cells, which leads to cancer development. Therefore, understanding the changes in CDK activity, cyclin-CDK assembly and the role of CDK inhibitors will help to understand the underlying regulatory processes in cell cycle progression, as well as provide a basis for the treatment of cancer and disease and the development of CDK inhibitor-based therapeutic agents. This review focuses on the key events of CDK activation or inactivation, and summarizes the regulatory processes of cyclin-CDK at specific times and locations, as well as the progress of research on relevant CDK inhibitor therapeutics in cancer and disease. The review concludes with a brief description of the current challenges of the cell cycle process, with the aim to provide scientific references and new ideas for further research on cell cycle process.

Key words:cyclin dependent kinase (CDK);cyclin;cyclin dependent kinase inhibitor (CKI);cancer;cell cycle