SPOP是一个重要的泛素E3连接酶，在肿瘤发生的过程中可能发挥着多重作用。之前报道认为SPOP在前列腺癌中抑制肿瘤发生，而在肾癌中促进肿瘤发生。但是为什么SPOP在不同的癌症中发挥相反的功能，目前尚不清楚。本实验室的前期工作发现组蛋白甲基化酶SETD2是SPOP的底物之一，SETD2是一个抑癌基因，SPOP可能通过降解SETD2促进肾癌的发生。同时，我们发现SPOP特异地在前列腺癌细胞而非肾癌细胞中降解CCNE1。CCNE1是细胞周期调控的关键cyclin之一，在多种肿瘤中是重要癌基因之一。我们将深入研究SPOP在前列腺癌细胞中调控CCNE1稳定性的分子机制，及在细胞周期和肿瘤发生中的作用。另外，我们还将比较研究SPOP在肾癌和前列腺癌中所调控的蛋白稳定性、基因表达、相互作用蛋白和信号通路的差异，揭示SPOP选择性调控肿瘤发生的分子机制，为下一步的临床应用研究提供理论基础。

SPOP is an important ubiquitin E3 ligase, which plays multiple functions in tumorigenesis. It was reported previously that SPOP represses tumor formation in prostate cancer, while promotes tumorigenesis in kidney cancer. However, it is not clear why SPOP plays opposite roles in different cancers. In the previous study, we found that histone methyltransferase SETD2 is one of the substrates for SPOP. SETD2 is a tumor suppressor and SPOP possibly promotes tumorigenesis in kidney cancer through SETD2 degradation. Currently, we further discovered that SPOP targets CCNE1 specifically in prostate cancer cells, but not in kidney cancer cells. We will further study the molecular mechanisms of CCNE1 stability regulated by SPOP and its roles in modulating cell cycle and tumorigenesis. Meanwhile, we will investigate the different impacts of SPOP on gene expression, associated proteins and signal transduction in kidney and prostate cancers, to reveal the molecular mechanisms for SPOP selectively regulating tumorigenesis, and provide theoretical foundation for further clinical studies.