Wing Simon S
Polypeptide Laboratory, Department of Medicine, Strathcona Anatomy & Dentistry Building, Room W315, 3640 University Street, McGill University, Que., H3A 2B2, Montreal, Canada.
Int J Biochem Cell Biol. 2003 May;35(5):590-605. doi: 10.1016/s1357-2725(02)00392-8.
Ubiquitination of proteins is now recognized to target proteins for degradation by the proteasome and for internalization into the lysosomal system, as well as to modify functions of some target proteins. Although much progress has been made in characterizing enzymes that link ubiquitin to proteins, our understanding of deubiquitinating enzymes is less developed. These enzymes are involved in processing the products of ubiquitin genes which all encode fusion proteins, in negatively regulating the functions of ubiquitination (editing), in regenerating free ubiquitin after proteins have been targeted to the proteasome or lysosome (recycling) and in salvaging ubiquitin from possible adducts formed with small molecule nucleophiles in the cell. A large number of genes encode deubiquitinating enzymes suggesting that many have highly specific and regulated functions. Indeed, recent findings provide strong support for the concept that ubiquitination is regulated by both specific pathways of ubiquitination and deubiquitination. Interestingly, many of these enzymes are localized to subcellular structures or to molecular complexes. These localizations play important roles in determining specificity of function and can have major influences on their catalytic activities. Future studies, particularly aimed at characterizing the interacting partners and potential substrates in these complexes as well as at determining the effects of loss of function of specific deubiquitinating enzymes will rapidly advance our understanding of the important roles of these enzymes as biological regulators.
蛋白质的泛素化如今被认为可将蛋白质靶向蛋白酶体进行降解、靶向溶酶体系统进行内化，以及修饰某些靶蛋白的功能。尽管在表征将泛素连接到蛋白质的酶方面已取得很大进展，但我们对去泛素化酶的了解仍较少。这些酶参与处理泛素基因的产物（所有泛素基因均编码融合蛋白），负向调节泛素化功能（编辑），在蛋白质被靶向蛋白酶体或溶酶体后再生游离泛素（循环利用），以及从细胞中与小分子亲核试剂形成的可能加合物中挽救泛素。大量基因编码去泛素化酶，这表明许多去泛素化酶具有高度特异性和受调控的功能。事实上，最近的研究结果为泛素化由泛素化和去泛素化的特定途径共同调控这一概念提供了有力支持。有趣的是，这些酶中的许多定位于亚细胞结构或分子复合物。这些定位在决定功能特异性方面发挥重要作用，并且可能对其催化活性产生重大影响。未来的研究，特别是旨在表征这些复合物中的相互作用伙伴和潜在底物，以及确定特定去泛素化酶功能丧失的影响，将迅速推进我们对这些酶作为生物调节剂的重要作用的理解。
