Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.
Biochim Biophys Acta Rev Cancer. 2017 Dec;1868(2):456-483. doi: 10.1016/j.bbcan.2017.09.002. Epub 2017 Sep 18.
The initial experiments performed by Rose, Hershko, and Ciechanover describing the identification of a specific degradation signal in short-lived proteins paved the way to the discovery of the ubiquitin mediated regulation of numerous physiological functions required for cellular homeostasis. Since their discovery of ubiquitin and ubiquitin function over 30years ago it has become wholly apparent that ubiquitin and their respective ubiquitin modifying enzymes are key players in tumorigenesis. The human genome encodes approximately 600 putative E3 ligases and 80 deubiquitinating enzymes and in the majority of cases these enzymes exhibit specificity in sustaining either pro-tumorigenic or tumour repressive responses. In this review, we highlight the known oncogenic and tumour suppressive effects of ubiquitin modifying enzymes in cancer relevant pathways with specific focus on PI3K, MAPK, TGFβ, WNT, and YAP pathways. Moreover, we discuss the capacity of targeting DUBs as a novel anticancer therapeutic strategy.
罗斯、赫什科和切哈诺沃最初进行的实验描述了在短寿命蛋白质中鉴定特定降解信号的方法，为发现泛素介导的众多对细胞内稳态至关重要的生理功能的调节铺平了道路。自 30 多年前发现泛素及其功能以来，泛素及其各自的泛素修饰酶显然是肿瘤发生的关键因素。人类基因组大约编码 600 种推定的 E3 连接酶和 80 种去泛素化酶，在大多数情况下，这些酶在维持促肿瘤或肿瘤抑制反应方面具有特异性。在这篇综述中，我们重点介绍了泛素修饰酶在癌症相关途径中的致癌和肿瘤抑制作用，特别是在 PI3K、MAPK、TGFβ、WNT 和 YAP 途径中的作用。此外，我们还讨论了靶向 DUBs 作为一种新的抗癌治疗策略的潜力。
