CIDE家族蛋白（Cidea、Cideb及Cidec）是一类通过介导脂滴融合增大来调控脂代谢的脂滴结合蛋白；其功能紊乱会影响细胞的储脂能力并破坏脂稳态，从而引发多种代谢性疾病。我们先前的研究发现Cidea和Cidec通过泛素-蛋白酶体进行降解，而且其降解受脂肪酸调控；然而，负责CIDE家族蛋白泛素化降解的泛素连接酶是未知的，且脂肪酸调控该家族蛋白降解的分子机制尚不明确。本项目拟对CIDE家族蛋白泛素化降解的调控机制和功能进行研究。我们已通过质谱筛选得到了Cidec蛋白的候选泛素连接酶，接下来我们将对CIDE家族蛋白的泛素连接酶进行鉴定并研究二者的相互作用；同时研究CIDE家族蛋白泛素化降解在脂代谢中的作用，并探讨脂肪酸调控CIDE家族蛋白泛素化降解的分子机制。本项目研究成果将从蛋白质翻译后修饰层面进一步揭示脂滴融合更为完整的分子调控机制，也为代谢性疾病的治疗提供新的理论基础和策略。

CIDE family proteins, including Cidea, Cideb and Cidec, are a class of lipid droplet (LD) binding proteins that regulate lipid metabolism by mediating LD fusion and growth. Their dysfunction affects the capacity of lipid storage in cells and impairs lipid homeostasis, resulting in the occurrence and development of many metabolic diseases. Previously, we have demonstrated that Cidea and Cidec are degraded through the ubiquitin-proteasome system and their degradation is regulated by fatty acids. However, the E3 ubiquitin ligases of CIDE family proteins are yet to be identified, and the molecular mechanism regulated by fatty acids remains to be elucidated. In this project, we plan to investigate the mechanism and function of ubiquitination-mediated degradation of CIDE family proteins. We have screened out several candidates of E3 ubiquitin ligases of Cidec by mass spectrometry. In this work, we will identify the E3 ubiquitin ligases of CIDE family proteins and study the interactions between them. Furthermore, we will investigate the functional effect of CIDE proteins ubiquitination-mediated degradation on lipid metabolism and the molecular mechanism regulated by fatty acids. This project will reveal the more comprehensive mechanism of LD fusion from the aspect of protein post-translational modification, and provide novel insights into the pathogenesis and new therapeutic strategies of metabolic diseases.