ArticleNature communications2023
USP25 regulates KEAP1-NRF2 anti-oxidation axis and its inactivation protects acetaminophen-induced liver injury in male mice.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Ovarian tumor domain-containing protein 1 deficiency attenuates metabolic dysfunction-associated steatotic liver disease by promoting the ubiquitination of HSP90α in hepatocytes.Molecular biomedicine · 2026Article
- The deubiquitinase YOD1 in renal tubular epithelial cells promotes diabetic kidney disease by stabilizing KEAP1.Acta pharmacologica Sinica · 2026Article
- BMSC-derived exosomal METTL3 synergizes with Sevoflurane to inhibit ferroptosis in pulmonary ischemia/reperfusion injury by enhancing USP7 N6-methyladenosine modification.Apoptosis : an international journal on programmed cell death · 2026Article
- CUL7-mediated KEAP1 ubiquitination promotes the progression of colon cancer via NRF2 signaling.Cell death & disease · 2026Article
- USP25 regulates atherosclerosis by restricting RIPK1-mediated inflammatory responses.EBioMedicine · 2026Article
- Covalent modification of Keap1 Cys489 by NU6300 activates Nrf2 signaling and suppresses NLRP3 inflammasome-mediated pyroptosis.Journal of pharmaceutical analysis · 2026Article
- Melatonin alleviates gentamicin-induced acute kidney injury through the Keap1/Nrf2/HO-1 signaling pathway.Biochemistry and biophysics reports · 2026Article
- Procyanidin Capsules Combat ALF by Restoring Mitochondrial Homeostasis and Inhibiting Necroptosis via the PGAM5/DRP1/PINK1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- USP25 inhibition ameliorates Parkinson's disease by restoring mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ubiquitin-specific protease 25: a new regulator for cardiovascular and cerebrovascular diseases.Frontiers in cell and developmental biology · 2026Review
- Subchronic Alcohol Exposure Exacerbates Acetaminophen-Induced Acute Liver Injury via Macrophage-Mediated Inflammation and Mitochondrial Dysfunction.Mediators of inflammation · 2026Article
- Triptolide inhibits ovarian cancer growth and metastasis via reprogramming of tumor-associated macrophages.Cell stress · 2026Article
- Gamma-aminobutyric acid attenuates cortisol-induced damage in human colorectal adenocarcinoma cells via Nrf2 signaling.Die Naturwissenschaften · 2025Article
- Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025Review
- Targeting Irgm1 to combat osteoporosis: suppressing ROS and restoring bone remodeling.Cell death & disease · 2025Article
- Major Ozonated Autoheamotherapy Alleviates Skeletal Muscle Ischemia/Reperfusion Injury by Regulating Nrf2/HO-1 Pathway.The Kaohsiung journal of medical sciences · 2025Article
- Rosmarinic Acid Protects Against Acetaminophen-Induced Hepatotoxicity by Suppressing Ferroptosis and Oxidative Stress Through Nrf2/HO-1 Activation in Mice.Marine drugs · 2025Article
- Engineered Spirulina platensis for treating rheumatoid arthritis and restoring bone homeostasis.Nature communications · 2025Article
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- The deubiquitinase USP28 maintains the expression of PPARγ and its inactivation protects mice from diet-induced MASH and hepatocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor responsible for mounting an anti-oxidation gene expression program to counter oxidative stress. Under unstressed conditions, Kelch-like ECH-associated protein 1 (KEAP1), an adaptor protein for CUL3 E3 ubiquitin ligase, mediates NRF2 ubiquitination and degradation. We show here that the deubiquitinase USP25 directly binds to KEAP1 and prevents KEAP1's own ubiquitination and degradation. In the absence of Usp25 or if the DUB is inhibited, KEAP1 is downregulated and NRF2 is stabilized, allowing the cells to respond to oxidative stress more readily. In acetaminophen (APAP) overdose-induced oxidative liver damage in male mice, the inactivation of Usp25, either genetically or pharmacologically, greatly attenuates liver injury and reduces the mortality rates resulted from lethal doses of APAP.
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