Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response.
Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response.
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DOI：
10.1016/j.jbc.2021.101077
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Silva GM
中科院分区：
文献类型：
--
作者：
Snyder NA;Silva GM
泛素信号传导是一个保守、广泛和动态的过程，其中蛋白质底物被泛素快速修饰，以影响蛋白质活性、定位或稳定性。为了调节这一过程，去泛素化酶 (DUB) 通过从这些底物中去除泛素来对抗泛素缀合酶和连接酶诱导的信号。许多 DUB 利用保守的泛素键断裂机制选择性地调节生理途径。 DUB 活性在动态环境中通过蛋白质-蛋白质相互作用、翻译后修饰和重新定位受到高度调节。 DUB 最大的家族半胱氨酸蛋白酶也对氧化应激的调节敏感，因为活性氧 (ROS) 直接修饰其酶活性所需的催化半胱氨酸。目前的研究表明 DUB 活性与人类疾病有关，包括各种癌症和神经退行性疾病。由于其选择性和功能作用，DUB 已成为治疗这些疾病的治疗开发的重要靶标。本综述将讨论 DUB 的主要类别及其调节机制，特别关注 DUB 氧化还原调节及其在氧化应激过程中的生理影响。
Ubiquitin signaling is a conserved, widespread, and dynamic process in which protein substrates are rapidly modified by ubiquitin to impact protein activity, localization, or stability. To regulate this process, deubiquitinating enzymes (DUBs) counter the signal induced by ubiquitin conjugases and ligases by removing ubiquitin from these substrates. Many DUBs selectively regulate physiological pathways employing conserved mechanisms of ubiquitin bond cleavage. DUB activity is highly regulated in dynamic environments through protein–protein interaction, posttranslational modification, and relocalization. The largest family of DUBs, cysteine proteases, are also sensitive to regulation by oxidative stress, as reactive oxygen species (ROS) directly modify the catalytic cysteine required for their enzymatic activity. Current research has implicated DUB activity in human diseases, including various cancers and neurodegenerative disorders. Due to their selectivity and functional roles, DUBs have become important targets for therapeutic development to treat these conditions. This review will discuss the main classes of DUBs and their regulatory mechanisms with a particular focus on DUB redox regulation and its physiological impact during oxidative stress.
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