pVHL是一个经典的肿瘤抑制因子，VHL基因的突变会导致多种肿瘤的发生，但是对于其中的分子机制并不十分清楚。FOXO3a是重要的转录因子，可以通过调节一系列参与细胞周期调控、细胞凋亡等相关基因的表达，进而决定细胞命运。同时，FOXO3a还是应答氧化损伤重要的转录因子，可以通过清除氧自由基来保护细胞免受氧化损伤。在前期的研究中，我们发现氧化损伤可以诱导pVHL的表达，并且这种诱导是依赖于FOXO3a的。此外，pVHL还与FOXO3a相互结合，并激活FOXO3a的转录活性。这些初始结果不仅提示了氧化应激对pVHL的表达调控，也表明了pVHL可能在氧化应激途径中具有重要的新功能。本项目拟在前期工作的基础上，深入阐明pVHL在FOXO3a介导的氧化损伤应答进程中的作用及其分子机制，为深入理解pVHL在肿瘤发生和发展过程中的作用机制，为相关肿瘤的早期诊断、预防和药物筛选提供有益的理论指导。

VHL(Von Hippel-Lindau) is a classic tumor suppressor，whose mutations lead to kinds of tumor. FOXO3a is an important transcriptional factor which determines cell fate via regulating the expression of target genes participated in the regulation of cell cycle, apoptosis, and so on. Meanwhile, FOXO3a is also a major factor which can protect cells from oxidative stress through the cleavage of oxygen-free radicals. In our previous study, we found that oxidative stress could induce the expression of pVHL, and the induction was dependent of FOXO3a. In addition, pVHL interacts with FOXO3a and activates its transactivity. These results not only provide a new kind of regulation of the expression of pVHL , but also indicate that pVHL may have an important role in oxidative stress. Here, we propose to further investigate the role and molecular mechanisms of pVHL in FOXO3a-mediated oxidative stress pathway and provide valuable instruction for diagnosis, prevention and drug screening of tumors.