细胞周期调节家族成员(Spy1)在细胞周期调控和肿瘤的发生发展过程中发挥着关键作用。本课题组先前研究表明，Spy1蛋白可直接结合并活化CDK2，促进肝细胞肝癌（HCC）的进程；课题组预实验发现Spy1-CDK2复合物可直接结合并磷酸化有丝分裂关键调控蛋白Sept2。Sept2能够通过调节微管蛋白调节G2/M期的转换。基于此，课题组提出Spy1-CDK2复合物可通过活化Sept2促进HCC细胞G2/M期的转换和HCC进程的假说。本课题拟：在HCC组织中阐明Spy1、CDK2及Sept2的表达关系；分析Spy1-CDK2复合物对Sept2的直接磷酸化作用，及磷酸化的Sept2通过微管蛋白对G2/M期转化的调节机制；在裸鼠动物模型中验证Spy1-CDK2通过活化Sept2对HCC发生发展的影响。验证结果将为进一步揭示G2/M期调节的分子机制，并为HCC的靶向治疗提供新的理论依据。

Cell Cycle Regulator Family Member(Spy1) plays an important role in cell cycle regulation and the development of human cancers. Our previous study indicates that Spy1 serves as a novel CDK2 activator through direct binding of CDK2, thereby promoting the progression of hepatocellular carcinoma(HCC). In the present study, we identified that Spy1-CDK2 complex can directly bind to and phosphorylate Sept2, a key organizer of the cytokinetic machinery. Sept2 is able to adjust the transformation of G2 / M phase by regulating tubulin.Given these findings, we proposed the hypothesis that Spy1-CDK2 complex promotes the transition of G2/M through direct phosphorylation and activation of Sept2 and faciliates the cell cycle progression of HCC cells. We aim to first clarify the correlation among the expression of Spy1, CDK2 and Sept2 in HCC clinical specimens. Next, we will determine the direct phosphorylation of Spy1-CDK2 on Sept2, and analyze the impact of Spy1-CDK2 mediated Spet2 phosphorylation on the transition of G2/M. Finally, we will investigate the role of Spy1-CDK2 complex on the progression of HCC via the phosphorylation of Sept2 using nude mouse model. Our study may help gain a better insight into the machonism underlying the transition of G2/M and provide new theoretical basis for targeted therapy of liver cancer.