Cellular and Molecular Physiology, Institute of Translational Medicine, and Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
Physiol Rev. 2013 Jul;93(3):1289-315. doi: 10.1152/physrev.00002.2013.
Ubiquitylation is a major posttranslational modification that controls most complex aspects of cell physiology. It is reversed through the action of a large family of deubiquitylating enzymes (DUBs) that are emerging as attractive therapeutic targets for a number of disease conditions. Here, we provide a comprehensive analysis of the complement of human DUBs, indicating structural motifs, typical cellular copy numbers, and tissue expression profiles. We discuss the means by which specificity is achieved and how DUB activity may be regulated. Generically DUB catalytic activity may be used to 1) maintain free ubiquitin levels, 2) rescue proteins from ubiquitin-mediated degradation, and 3) control the dynamics of ubiquitin-mediated signaling events. Functional roles of individual DUBs from each of five subfamilies in specific cellular processes are highlighted with an emphasis on those linked to pathological conditions where the association is supported by whole organism models. We then specifically consider the role of DUBs associated with protein degradative machineries and the influence of specific DUBs upon expression of receptors and channels at the plasma membrane.
泛素化是一种主要的翻译后修饰，控制着细胞生理的大多数复杂方面。它通过一大类去泛素化酶（DUBs）的作用被逆转，这些酶作为许多疾病状况的有吸引力的治疗靶点正在出现。在这里，我们对人类 DUB 的组成进行了全面的分析，指出了结构基序、典型的细胞拷贝数和组织表达谱。我们讨论了如何实现特异性以及 DUB 活性如何被调节。一般来说，DUB 的催化活性可以用于 1）维持游离泛素水平，2）从泛素介导的降解中拯救蛋白质，3）控制泛素介导的信号事件的动力学。强调了来自五个亚家族的每个 DUB 在特定细胞过程中的功能作用，特别强调了那些与整个生物体模型支持的病理状况相关的作用。然后，我们特别考虑了与蛋白降解机制相关的 DUB 的作用，以及特定的 DUB 对质膜上受体和通道表达的影响。
