文章：

癌症中的去泛素酶

Deubiquitinases in cancer

原文发布日期：2023-11-07

DOI: 10.1038/s41568-023-00633-y

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

泛素化是大多数（若非全部）信号通路的重要调节机制，而细胞信号传导缺陷在癌症发生、进展及最终转移过程中居于核心地位。E3泛素连接酶介导的泛素信号标记过程会被人类体内约100种去泛素化酶（DUBs）的作用直接抵消。DUBs与E3连接酶通过协同作用于不同底物和/或泛素信号，共同调控泛素信号传导。泛素化与去泛素化之间的平衡受到精密调控，以确保蛋白质稳态的协调运作及对细胞刺激与应激源的有效响应。因此，DUBs与所有癌症特征相关并不令人意外。这些关联往往复杂且多维度，具体表现为：多种DUBs参与特定癌症特征，单个DUBs影响多条癌症相关通路，且根据环境与肿瘤类型差异，同一DUB可能兼具促癌与抑癌的双重活性。尽管相关研究仍显不足，但对DUB在癌症生理学中功能的日益深入理解，终将明确哪些DUB需要特异性抑制或激活——这两种干预策略如今均已具备可行性。通过系统评估DUB调控在相关癌症模型中的生理效应，最终将能精准识别最可能受益于DUB靶向治疗的患者群体。

原文链接：

Deubiquitinases in cancer