乙酰辅酶A羧化酶2（Acetyl CoA Carboxylase 2, ACC2）是治疗糖尿病和肥胖症的重要药物靶标，抑制其活力可以增加脂肪酸氧化，有效降低动物体内的血糖水平。前人的研究都是以筛选ACC2的小分子抑制剂为主，但这类小分子具有强烈的疏水性，目前还未应用于临床。本研究基于前期的研究方法，发现泛素E3连接酶E6AP可以泛素化降解ACC2，因此，我们提出从ACC2本身的降解机制出发，力图开辟一条“通过泛素化降解ACC2的抗糖尿病”新途径。拟通过多种细胞生物学实验和动物实验，开展研究泛素连接酶E6AP对ACC2的泛素化降解调控机制，以及这种调控机制在糖尿病发病过程中的作用，为接下来深入探讨E6AP作为潜在的治疗糖尿病的新靶标提供一定的理论依据，也为以ACC2为靶点的糖尿病药物研发提供一些新思路。

Acetyl-coenzyme A carboxylase 2 (ACC2) has crucial roles in fatty acid metabolism. Inhibition of acetyl-CoA carboxylase 2, which results in inhibition of fatty acid synthesis and stimulation of fatty acid oxidation, has the potential to favorably affect the level of blood glucose in mice. Current drug discovery of ACC2 is mostly focused on the inhibition of ACC2 by using a small molecule. However, due to the strong hydrophobic property of these small molecule inhibitors, there are no any drug available in clinical application. In this study, we found the ubiquitin E3 ligase E6AP could specifically degrade ACC2 through the ubiquitin-proteasome system. We propose to start from the degradation mechanism of ACC2 itself，and explore a new approach of "anti-diabetes by ubiquitination of ACC2". The mechanism of the degradation of ACC2 by E6AP will be investigated in both cell lines and diabetes mouse models. It provides a theoretical basis for further exploration of E6AP as a potential new target for the treatment of diabetes. These results will also provide a new way for the drug discovery of diabetes related to ACC2.