Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 303 E. Superior Street, Chicago, IL 60611, USA.
Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Cancer Biology, University of Cincinnati, Cincinnati, OH.
Curr Opin Cell Biol. 2019 Jun;58:85-94. doi: 10.1016/j.ceb.2019.02.008. Epub 2019 Mar 18.
Ubiquitination is a versatile and tightly regulated post-translational protein modification with many distinct outcomes affecting protein stability, localization, interactions, and activity. Ubiquitin chain linkages anchored on substrates can be further modified by additional post-translational modifications, including phosphorylation and SUMOylation. Deubiquitinases (DUBs) reverse these ubiquitin marks with matched levels of precision. Over hundred known DUBs regulate a wide variety of cellular events. In this review, we focus on ubiquitin-specific protease 7 (USP7, also known as herpesvirus-associated ubiquitin-specific protease, or HAUSP) as one of the best studied, disease-associated DUBs. By highlighting the functions of USP7, particularly in the nucleus, and the emergence of the newest generation of USP7 inhibitors, we illustrate the importance of individual DUBs in the nucleus, and the therapeutic prospects of DUB targeting in human disease.
泛素化是一种具有多种不同结果的多功能且严格调控的翻译后蛋白质修饰，影响蛋白质稳定性、定位、相互作用和活性。锚定在底物上的泛素链连接可以通过其他翻译后修饰进一步修饰，包括磷酸化和 SUMO 化。去泛素化酶（DUB）以匹配的精度逆转这些泛素标记。已知的超过一百种 DUB 调节着各种各样的细胞事件。在这篇综述中，我们重点介绍泛素特异性蛋白酶 7（USP7，也称为疱疹病毒相关泛素特异性蛋白酶或 HAUSP），它是研究最多的、与疾病相关的 DUB 之一。通过强调 USP7 的功能，特别是在核内的功能，以及新一代 USP7 抑制剂的出现，我们说明了核内单个 DUB 的重要性，以及靶向 DUB 在人类疾病中的治疗前景。
