ACTH型垂体瘤是脑内垂体瘤的一种亚型，通过分泌大量的促肾上腺皮质激素，导致皮质醇增多症和非常严重临床症候群(又称为库欣病)。库欣病的诊疗非常复杂，缺乏有效的靶向药物，是目前最棘手的一类垂体瘤。最近，我们发现去泛素化酶USP8在ACTH型垂体瘤中存在高频突变。然而，USP8突变在ACTH型垂体瘤中致病的分子机制尚未完全研究清楚。我们前期的工作初步证明选择性自噬接头分子p62是USP8新的底物分子。本项目将深入研究USP8调控p62的分子机制，以及这条通路在ACTH型垂体瘤中的具体作用。这项研究将丰富USP8相关联的信号网络，有助于深入理解USP8突变在ACTH型垂体瘤中致病的具体分子机制，最终为库欣病的诊疗提供理论指导。

ACTH pituitary tumor is a subtype of pituitary tumor, which causes Cushing’s syndrome. Cushing’s syndrome is a serious endocrine disorder, mainly caused by endogenous glucocorticoid excess. ACTH pituitary tumor leads to hypercortisolism and very severe clinical syndrome by over-secreting adrenocorticotropin(ACTH). Making the diagnosis and treatment of Cushing’s syndrome is difficult because no one physical finding is pathognomonic and many of the symptoms and physical findings occur in a large percentage of the general population. Recently, we revealed that USP8 gene has high frequency mutation in human ACTH pituitary tumor samples by exome sequencing technology. However, the molecular mechanism of pathogenesis regulated by USP8 in ACTH pituitary is not completely clear yet. By using yeast two hybrid method and a variety of biochemical methods, we have identified the selective autophagy adaptor molecule p62 as a new substrate of USP8. Our research aims at understanding the molecular mechanism of USP8-p62 signal pathway in regulating the growth of ACTH pituitary tumor. This project will enrich the research of USP8 correlated signal network, and help us understand the regulatory role of USP8 in pathogenesis in ACTH pituitary tumor, in order to provide theoretical guidance for the diagnosis and treatment of Cushing's syndrome.