CUEDC2调控细胞周期G1/S期转化及细胞生长的机制研究

恶性肿瘤以细胞周期稳态失控为主要特征，G1/S期转化调控异常是导致肿瘤细胞基因组非稳定性及异常增殖的重要原因。CUEDC2是本实验室近年发现的一个重要功能蛋白。前期研究发现，CUEDC2在细胞有丝分裂纺锤体检查点调控中发挥重要功能（2011，Nature Cell Biology）。在此重要进展基础上，近期结果表明CUEDC2参与细胞周期G1/S检查点调控，干涉CUEDC2延缓G1/S期转化并显著影响细胞生长增殖。基于以上线索，本项目拟进一步利用干涉、过表达细胞系及转基因、敲除动物模型结合周期分析、蛋白检测等手段，深入阐明CUEDC2在G1/S期转化、细胞生长及肿瘤发生发展中的功能并揭示其调控机理。本项目的实施将鉴定出一个新的G1/S期调控分子，进一步拓展人们对细胞周期调控和癌变关系的认识，为临床诊断和指导治疗提供重要的理论依据。

Uncontrolled cell cycle progression is the major feature of tumor. Deregulation of G1/S transition contributes largely to genome instability and abnormally cell proliferation. CUEDC2 is a novel protein identified by our lab and its function has not been well understood. Previous work from our lab showed that CUEDC2 plays critical role in metaphase progression and involves in spindle checkpoint regulation. In recent study, we found that CUEDC2 degradated in DNA damage induced G1 arrest, and might be participated in G1/S checkpoint activation. Knock down of CUEDC2 leads to much delay of G1/S progression and inhibition of cell proliferation. Nextly,in this project，we would use the prepared CUEDC2 knock down or overexpression stable cell lines and CUEDC2 knock out mouse model to explore the detailed mechanism of how CUEDC2 functions in G1/S transition and tumor development, which would provide important insight into the critical roles of CUEDC2 in cell cycle checkpoint regulation and tumor development.