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Updated: Oct 12, 2025
Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples
Published on: May 10, 2015
Redox regulation of DUBs and its therapeutic implications in cancer
Apoorvi Tyagi1, Saba Haq2, Suresh Ramakrishna3
1Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, 04763, South Korea.
Abstract:
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.
Insights
Reactive oxygen species (ROS) are crucial in cancer. This review highlights how ROS regulate deubiquitinating enzymes (DUBs) through oxidation, offering potential new anticancer therapeutic strategies.
Area of Science:
- Oncology
- Biochemistry
- Cellular Biology
Background:
- Reactive oxygen species (ROS) play a dual role in cancer, with low levels being beneficial and excessive accumulation promoting cancer progression.
- Cancer cells maintain ROS homeostasis through antioxidant defense systems, but imbalances drive disease progression.
- Post-translational modifications, including ubiquitination, are critical for managing ROS levels.
Purpose of the Study:
- To review recent findings on ROS-mediated signaling in cancer.
- To emphasize the regulation of deubiquitinating enzymes (DUBs) by ROS-induced oxidation.
- To propose future research directions for anticancer therapeutics targeting ROS-DUB interactions.
Main Methods:
- Literature review of recent studies on ROS, cancer, and DUBs.
- Analysis of mechanisms linking ROS to DUB activity and regulation.
- Synthesis of current knowledge on ROS-induced modifications of DUBs.
Main Results:
- Elevated ROS levels in cancer disrupt cellular signaling and promote progression.
- ROS reversibly inactivate DUBs via oxidation of their catalytic cysteine residues.
- This oxidative regulation of DUBs influences various cellular events relevant to cancer.
Conclusions:
- Understanding ROS-mediated DUB regulation is key to cancer biology.
- Targeting ROS modulation of DUBs presents a promising avenue for novel anticancer therapies.
- Further research into ROS-induced DUB modifications could uncover new therapeutic strategies.
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