Institute of Cancer Sciences, University of Glasgow, United Kingdom; The CRUK Beatson Institute, Glasgow, Switchback Road, G61 1BD, United Kingdom; Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt.
Int J Biochem Cell Biol. 2018 Aug;101:80-93. doi: 10.1016/j.biocel.2018.06.001. Epub 2018 Jun 1.
Dynamic modulation and posttranslational modification of proteins are tightly controlled biological processes that occur in response to physiological cues. One such dynamic modulation is ubiquitination, which marks proteins for degradation via the proteasome, altering their localization, affecting their activity, and promoting or interfering with protein interactions. Hence, ubiquitination is crucial for a plethora of physiological processes, including cell survival, differentiation and innate and adaptive immunity. Similar to kinases, components of the ubiquitination system are often deregulated, leading to a variety of diseases, such as cancer and neurodegenerative disorders. In a context-dependent manner, ubiquitination can regulate both tumor-suppressing and tumor-promoting pathways in cancer. This review outlines how components of the ubiquitination systems (e.g. E3 ligases and deubiquitinases) act as oncogenes or tumor suppressors according to the nature of their substrates. Furthermore, I interrogate how the current knowledge of the differential roles of ubiquitination in cancer lead to technical advances to inhibit or reactivate the components of the ubiquitination system accordingly.
蛋白质的动态调节和翻译后修饰是对生理信号做出反应的紧密控制的生物学过程。其中一种动态调节是泛素化，它通过蛋白酶体标记蛋白质进行降解，改变其定位，影响其活性，并促进或干扰蛋白质相互作用。因此，泛素化对于许多生理过程至关重要，包括细胞存活、分化以及先天和适应性免疫。与激酶类似，泛素化系统的组成部分经常失调，导致多种疾病，如癌症和神经退行性疾病。在依赖于上下文的情况下，泛素化可以调节癌症中的肿瘤抑制和促进途径。这篇综述概述了泛素化系统的组成部分（例如 E3 连接酶和去泛素化酶）如何根据其底物的性质作为癌基因或肿瘤抑制因子发挥作用。此外，我探讨了泛素化在癌症中的不同作用的现有知识如何导致技术进步，从而相应地抑制或重新激活泛素化系统的组成部分。
