Zhou Yuan, Chen Runzhe, Luo Xiaofang, Zhang Wei-Dong, Qin Jiang-Jiang
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Drug Discov Today. 2020 Sep 16. doi: 10.1016/j.drudis.2020.09.015.
Ubiquitination is a crucial post-translational modification (PTM) of proteins and regulates their stabilities and activities, thereby modulating multiple signaling pathways. UbcH5c, a member of the UbcH5 ubiquitin-conjugating enzyme (E2) protein family, engages in the ubiquitination of dozens of proteins and regulates nuclear factor kappa-B (NF-κB), p53 tumor suppressor, and several other essential signaling pathways. UbcH5c has been reported to be abnormally expressed in human cancer and immune disorders and is involved in the initiation and progression of these diseases. In this review, we mainly focus on UbcH5c structure, activity, signaling pathways, and its relevance to cancer and immune disorders. We end by integrating all known factors relating to UbcH5c inhibition as a potential cancer therapy method, and discuss associated challenges.
泛素化是蛋白质一种关键的翻译后修饰（PTM），可调节其稳定性和活性，从而调控多种信号通路。UbcH5c是UbcH5泛素结合酶（E2）蛋白家族的成员，参与数十种蛋白质的泛素化过程，并调控核因子κB（NF-κB）、p53肿瘤抑制因子以及其他几种重要的信号通路。据报道，UbcH5c在人类癌症和免疫紊乱中异常表达，并参与这些疾病的发生和发展。在本综述中，我们主要关注UbcH5c的结构、活性、信号通路及其与癌症和免疫紊乱的相关性。最后，我们整合了与UbcH5c抑制作为一种潜在癌症治疗方法相关的所有已知因素，并讨论了相关挑战。
