泛素化是大多数（如果不是全部）信号通路的重要调节因子，细胞信号传导缺陷对于癌症的发生、进展和最终转移至关重要。 E3 泛素连接酶对泛素信号的附着与人体中大约 100 种去泛素化酶 (DUB) 的作用直接相反。 DUB 和 E3 连接酶通过提供对不同底物和/或泛素信号的选择性来协调泛素信号传导。泛素化和去泛素化之间的平衡受到精确控制，以确保正确协调蛋白质稳态以及对细胞刺激和应激源的反应。毫不奇怪，DUB 与癌症的所有特征都有关联。这些关系通常是复杂且多方面的，突出表现在某些标志中多个 DUB 的含义以及单个 DUB 对多种癌症相关途径的影响，有时根据背景和肿瘤类型具有对比的促进癌症和抑制癌症的活性。尽管尚未得到充分研究，但随着对癌症生理学中 DUB 功能的不断了解，最终将识别出需要特异性抑制或激活的 DUB，而这两种方法现在都是可行的。对相关癌症模型中 DUB 调节的生理后果的综合评估将最终确定最有可能从 DUB 靶向治疗中受益的患者群体。© 2023。Springer Nature Limited。

Ubiquitination is an essential regulator of most, if not all, signalling pathways, and defects in cellular signalling are central to cancer initiation, progression and, eventually, metastasis. The attachment of ubiquitin signals by E3 ubiquitin ligases is directly opposed by the action of approximately 100 deubiquitinating enzymes (DUBs) in humans. Together, DUBs and E3 ligases coordinate ubiquitin signalling by providing selectivity for different substrates and/or ubiquitin signals. The balance between ubiquitination and deubiquitination is exquisitely controlled to ensure properly coordinated proteostasis and response to cellular stimuli and stressors. Not surprisingly, then, DUBs have been associated with all hallmarks of cancer. These relationships are often complex and multifaceted, highlighted by the implication of multiple DUBs in certain hallmarks and by the impact of individual DUBs on multiple cancer-associated pathways, sometimes with contrasting cancer-promoting and cancer-inhibiting activities, depending on context and tumour type. Although it is still understudied, the ever-growing knowledge of DUB function in cancer physiology will eventually identify DUBs that warrant specific inhibition or activation, both of which are now feasible. An integrated appreciation of the physiological consequences of DUB modulation in relevant cancer models will eventually lead to the identification of patient populations that will most likely benefit from DUB-targeted therapies.© 2023. Springer Nature Limited.