白内障是全球首要致盲性疾病，包括先天性白内障和非遗传性白内障。已有研究表明多种应激因素诱导的晶状体上皮细胞凋亡是非遗传性白内障形成的共同细胞学基础。蛋白质SUMO化是真核生物中重要的调控机制，对晶状体发育起着关键作用。我们前期研究表明蛋白质SUMO E3连接酶PIAS1参与调节晶状体上皮细胞的凋亡。机制上，我们初步发现在晶状体上皮细胞中PIAS1介导p53的SUMO化，并调节其下游促凋亡蛋白Bax的表达水平。因此，本项目将利于现代分子生物学方法，确定（1）PIAS1是否通过SUMO化调节p53的活性和功能；（2）PIAS1是否通过SUMO化调节Bax的活性和功能；（3）PIAS1是否通过p53和Bax的SUMO化调节晶状体上皮细胞的凋亡和白内障的发生。这些结果为进一步了解白内障的发病机制带来崭新的信息，并为其治疗提供新的切入点。

Cataract is the leading cause of blindness in the world, including congenital cataracts and non-hereditary cataracts. Studies have shown that the apoptosis of lens epithelial cells induced by various stress factors is a common cytological basis for non-hereditary cataract formation. Protein sumoylation is an important regulatory mechanism in eukaryotes, playing a key role in the development of lens. Our previous studies have shown that the SUMO E3 ligase PIAS1 is involved in regulating apoptosis of lens epithelial cells. Regarding its action mechanism, our preliminary data suggest that PIAS1 functions as a SUMO ligase toward p53 sumoylation in lens epithelial cells and regulates the expression level of its downstream pro-apoptotic protein Bax. Therefore, in this project，we will utilize modern molecular and cellular biology methodology to determine (1) whether PIAS1 regulates the activity and function of p53 through sumoylation; (2) whether PIAS1 regulates the activity and function of Bax by sumoylation ;(3) whether PIAS1 regulates lens epithelial cell apoptosis and cataractogenesis through sumoylation of p53 and Bax. These results bring new information to further understand the pathogenesis of cataract and provide a new entry point for its treatment.