Deubiquitylating enzymes (DUBs) are proteases that remove the ubiquitin moiety from ubiquitylated substrates to antagonize the modification mediated by E3 ubiquitin ligases. Currently, DUBs have been found to play critical roles in the regulation of various physiological or pathological processes, such as embryogenesis, immune homeostasis, tumorigenesis and neurodegenerative diseases. Accumulating evidences have suggested that different DUBs exert distinct function such as oncogenic, tumor-suppressive or context-dependent roles in tumorigenesis, mainly by affecting the protein stability, enzymatic activity or subcellular localization of its substrates. Importantly, multiple potent inhibitors targeting the enzymatic activity of oncogenic DUBs have been developed and show promising anti-cancer efficacy in preclinical models. Thus, exploring the unique role of DUB enzymes and their downstream effectors will provide novel insights into the molecular basis of cancer development. Here, we review and summarize recent progress on DUB functional annotation, as well as its biochemical regulation, to provide a better understanding for cancer therapies by targeting DUBs.

去泛素化酶（DUB）是从泛素化的底物中去除泛素部分以拮抗E3泛素连接酶介导的修饰的蛋白酶。当前，已经发现DUB在各种生理或病理过程的调节中起关键作用，例如胚胎发生，免疫稳态，肿瘤发生和神经退行性疾病。越来越多的证据表明，不同的DUB在肿瘤发生中发挥独特的功能，例如致癌，抑制肿瘤或背景相关的作用，主要是通过影响其底物的蛋白质稳定性，酶活性或亚细胞定位来实现的。重要的是，已经开发了多种靶向致癌DUBs的酶活性的有效抑制剂，并在临床前模型中显示出有希望的抗癌功效。因此，探索DUB酶及其下游效应子的独特作用，将为癌症发展的分子基础提供新的见解。在这里，我们回顾并总结了DUB功能注释及其生化调节方面的最新进展，以针对DUB为目标，从而为癌症治疗提供了更好的理解。