细胞中活性氧自由基（ROS）的产生会导致氧化损伤的累积，促进细胞衰老的发生。超氧化物歧化酶（SOD）是细胞中重要的抗氧化酶，并且SOD1蛋白在细胞质中行使SOD酶清除超氧自由基的主要功能，降低细胞氧化损伤并减缓细胞衰老。SOD1蛋白功能的调控机制仍然有待阐明。我们发现SOD1蛋白可能存在一种新的类泛素化修饰—Ufmylation修饰，并影响细胞衰老的发生。前期工作中，我们已经证实SOD1蛋白与Ufmylation修饰关键组分UFM1和UFL1（E3酶）相互作用；敲低UFM1或UFL1后，SOD1蛋白水平降低，ROS水平升高；成纤维细胞中UFM1敲低可以促进细胞衰老。本项目拟研究SOD1蛋白Ufmylation修饰的分子机制，揭示Ufmylation修饰对SOD1蛋白功能的调控机制，阐明SOD1蛋白Ufmylation修饰在细胞衰老中的作用，为衰老相关疾病的诊断和治疗提供科学依据。

Generation of reactive oxygen species (ROS) results in the accumulation of oxidative damage and promotes cell senescence. Superoxide dismutase (SOD) serves as a major antioxidant in cells. And the role of SOD in degradation of superoxide free radical is mainly played by SOD1 in cytoplasm, reducing oxidative damage and retarding cell senescence. However, the underlying mechanisms of SOD1 function in cell senescence remain elusive. In our preliminary study, we found that SOD1 is a potential substrate of Ufmylation, a newly identified ubiquitination-like modification. We have demonstrated that SOD1 can interact with UFM1 and UFL1, which are critical components of Ufmylation system. Knockdown of UFM1 or UFL1 resulted in reduced SOD1 protein levels and increased ROS levels. Furthermore, UFM1 knockdown promotes cell senescence of human fibroblasts. Together, these data suggest that SOD1 is a novel target of Ufmylation modification. This project aims to understand the mechanistic function of SOD1 Ufmylation in cell senescence and to provide insights for drug target and therapy of age-related disease.