Tyagi Apoorvi, Haq Saba, Ramakrishna Suresh
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, 04763, South Korea.
Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 04763, South Korea.
Redox Biol. 2021 Nov 20;48:102194. doi: 10.1016/j.redox.2021.102194.
Reactive oxygen species (ROS) act as a double-edged sword in cancer, where low levels of ROS are beneficial but excessive accumulation leads to cancer progression. Elevated levels of ROS in cancer are counteracted by the antioxidant defense system. An imbalance between ROS generation and the antioxidant system alters gene expression and cellular signaling, leading to cancer progression or death. Post-translational modifications, such as ubiquitination, phosphorylation, and SUMOylation, play a critical role in the maintenance of ROS homeostasis by controlling ROS production and clearance. Recent evidence suggests that deubiquitinating enzymes (DUBs)-mediated ubiquitin removal from substrates is regulated by ROS. ROS-mediated oxidation of the catalytic cysteine (Cys) of DUBs, leading to their reversible inactivation, has emerged as a key mechanism regulating DUB-controlled cellular events. A better understanding of the mechanism by which DUBs are susceptible to ROS and exploring the ways to utilize ROS to pharmacologically modulate DUB-mediated signaling pathways might provide new insight for anticancer therapeutics. This review assesses the recent findings regarding ROS-mediated signaling in cancers, emphasizes DUB regulation by oxidation, highlights the relevant recent findings, and proposes directions of future research based on the ROS-induced modifications of DUB activity.
活性氧（ROS）在癌症中扮演着双刃剑的角色，低水平的ROS有益，但过量积累会导致癌症进展。癌症中升高的ROS水平会被抗氧化防御系统抵消。ROS生成与抗氧化系统之间的失衡会改变基因表达和细胞信号传导，导致癌症进展或死亡。翻译后修饰，如泛素化、磷酸化和SUMO化，通过控制ROS的产生和清除在维持ROS稳态中起关键作用。最近的证据表明，去泛素化酶（DUBs）介导的从底物上去除泛素受ROS调节。ROS介导的DUBs催化半胱氨酸（Cys）氧化，导致其可逆失活，已成为调节DUB控制的细胞事件的关键机制。更好地理解DUBs对ROS敏感的机制，并探索利用ROS药理学调节DUB介导的信号通路的方法，可能为抗癌治疗提供新的见解。本综述评估了关于癌症中ROS介导信号传导的最新发现，强调了氧化对DUB的调节，突出了相关的最新发现，并基于ROS诱导的DUB活性修饰提出了未来研究的方向。
