卵巢癌是死亡率最高的妇科恶性肿瘤，其发生发展的机制尚未明确。E3泛素连接酶Cdc20驱动正常的细胞周期进展，其表达失调在肿瘤发生发展中发挥重要作用。前期研究中，通过对癌症基因组图谱数据和临床样本分析，我们发现Cdc20在卵巢癌病人癌组织中表达升高；敲低Cdc20表达抑制卵巢癌细胞的生长。利用生物素pull down结合质谱技术，我们鉴定出Cdc20的相互作用蛋白REST。进一步研究发现Cdc20促进REST泛素化且敲低Cdc20提高REST的表达。据此提出假设：Cdc20通过泛素化降解REST，调控REST及其下游癌基因表达，促进卵巢癌的生长。我们将利用分子细胞生物学和生物化学的方法结合体外和小鼠实验探索和阐明Cdc20降解REST的分子机制和促肿瘤生长作用机制，为卵巢癌的发生及发展提供理论依据和新的治疗靶标。

Ovarian cancer is the most lethal gynecological malignancy, but under mechanism of development is largely unknown. The Anaphase Promoting Complex (APC) coactivator Cdc20 drives proper cell cycle progression and plays an important role in tumorigenesis. Recently, we found Cdc20 expression was increased by analysis The Cancer Genome Atlas (TCGA) and patient samples of ovarian cancer. Moreover, depletion of Cdc20 suppressed the proliferation of ovarian cancer cell lines. By Biotin pull-down and LC-MS/MS analysis, we identified REST that interacted with Cdc20.In addition, depletion of Cdc20 increased the expression of REST. Thus, we raise the hypothesis that Cdc20 promote ovarian cancer proliferation through targeting REST for destruction based on preliminary data. We will explore the molecular and function mechanisms of REST degradation and tumor development mediated by Cdc20 using integrated approaches including molecular cell biology and mouse model. This project focuses on which may provide a theoretical basis and potential targets for the clinical treatment of ovarian cancer.