Li Xiaolong, Yang Ge, Zhang Wenyao, Qin Biying, Ye Zifan, Shi Huijing, Zhao Xinmeng, Chen Yihang, Song Bowei, Mei Ziqing, Zhao Qi, Wang Feng
Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing, China.
School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China.
Front Cell Dev Biol. 2022 Apr 4;10:875124. doi: 10.3389/fcell.2022.875124. eCollection 2022.
As a deubiquitination (DUB) enzyme, ubiquitin-specific protease 13 (USP13) is involved in a myriad of cellular processes, such as mitochondrial energy metabolism, autophagy, DNA damage response, and endoplasmic reticulum-associated degradation (ERAD), by regulating the deubiquitination of diverse key substrate proteins. Thus, dysregulation of USP13 can give rise to the occurrence and development of plenty of diseases, in particular malignant tumors. Given its implications in the stabilization of disease-related proteins and oncology targets, considerable efforts have been committed to the discovery of inhibitors targeting USP13. Here, we summarize an overview of the recent advances of the structure, function of USP13, and its relations to diseases, as well as discovery and development of inhibitors, aiming to provide the theoretical basis for investigation of the molecular mechanism of USP13 action and further development of more potent druggable inhibitors.
作为一种去泛素化（DUB）酶，泛素特异性蛋白酶13（USP13）通过调节多种关键底物蛋白的去泛素化作用，参与了众多细胞过程，如线粒体能量代谢、自噬、DNA损伤反应和内质网相关降解（ERAD）。因此，USP13的失调会引发多种疾病的发生和发展，尤其是恶性肿瘤。鉴于其在疾病相关蛋白稳定和肿瘤学靶点方面的作用，人们已投入大量精力来发现靶向USP13的抑制剂。在此，我们综述了USP13的结构、功能及其与疾病的关系，以及抑制剂的发现与开发等方面的最新进展，旨在为研究USP13作用的分子机制以及进一步开发更有效的可成药抑制剂提供理论依据。
