Lei Hu, Wang Jiaqi, Hu Jiacheng, Zhu Qian, Wu Yingli
Department of Pathophysiology, International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Biomark Res. 2021 Aug 28;9(1):66. doi: 10.1186/s40364-021-00320-w.
Deubiquitinases (DUBs) are enzymes that control the stability, interactions or localization of most cellular proteins by removing their ubiquitin modification. In recent years, some DUBs, such as USP7, USP9X and USP10, have been identified as promising therapeutic targets in hematological malignancies. Importantly, some potent inhibitors targeting the oncogenic DUBs have been developed, showing promising inhibitory efficacy in preclinical models, and some have even undergone clinical trials. Different DUBs perform distinct function in diverse hematological malignancies, such as oncogenic, tumor suppressor or context-dependent effects. Therefore, exploring the biological roles of DUBs and their downstream effectors will provide new insights and therapeutic targets for the occurrence and development of hematological malignancies. We summarize the DUBs involved in different categories of hematological malignancies including leukemia, multiple myeloma and lymphoma. We also present the recent development of DUB inhibitors and their applications in hematological malignancies. Together, we demonstrate DUBs as potential therapeutic drug targets in hematological malignancies.
去泛素化酶（DUBs）是一类通过去除细胞内大多数蛋白质的泛素修饰来控制其稳定性、相互作用或定位的酶。近年来，一些DUBs，如USP7、USP9X和USP10，已被确定为血液系统恶性肿瘤中有前景的治疗靶点。重要的是，一些靶向致癌DUBs的强效抑制剂已被开发出来，在临床前模型中显示出有前景的抑制效果，有些甚至已经进入临床试验阶段。不同的DUBs在多种血液系统恶性肿瘤中发挥着不同的作用，如致癌、肿瘤抑制或依赖于背景的效应。因此，探索DUBs及其下游效应器的生物学作用将为血液系统恶性肿瘤的发生和发展提供新的见解和治疗靶点。我们总结了参与不同类型血液系统恶性肿瘤（包括白血病、多发性骨髓瘤和淋巴瘤）的DUBs。我们还介绍了DUB抑制剂的最新进展及其在血液系统恶性肿瘤中的应用。总之，我们证明了DUBs是血液系统恶性肿瘤中潜在的治疗药物靶点。
