ArticleCell death & disease2023
USP14 governs CYP2E1 to promote nonalcoholic fatty liver disease through deubiquitination and stabilization of HSP90AA1.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 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
- Unraveling Effects and Pharmacological Mechanisms of Phellodendrine on Inflammatory Bowel Disease.Biomolecules · 2026Article
- The mechanism of deubiquitinase USP14 modifying HSP90AA1 to activate NRF2 signaling in lung cancer cell resistance to ferroptosis.Molecular biology reports · 2026Article
- Article
- Grape Seed Oil Attenuates Myocardial Fibrosis by Inhibiting the PI3K/AKT Signaling Pathway.Foods (Basel, Switzerland) · 2026Article
- Network toxicology study and key target validation of chlorpyrifos-induced nonalcoholic fatty liver disease.Scientific reports · 2026Article
- <p>Anxiety‑induced overactive bladder: The role of oxidative stress and NF‑κB signaling pathway with Hsp90 as a potential biomarker</p>.Molecular medicine reports · 2026Article
- Deubiquitinases in liver diseases: from mechanisms to targeted therapy.Science China. Life sciences · 2026Review
- Spatial phosphoproteomics reveals regional phosphorylation features in liver cirrhosis progression.Journal of translational medicine · 2026Article
- Cartilage Intermediate Layer Protein 2 Aggravates Hepatic Lipid Accumulation and Inflammation Through the IRE1α/XBP1 Pathway.International journal of molecular sciences · 2026Article
- USP9X Promotes Hepatocellular Carcinoma Progression via Stabilization of HSP90AA1.Journal of hepatocellular carcinoma · 2026Article
- Hepatoprotective evaluation of benzoylated emodin derivatives: Integrating bioinformatics andBioMedicine · 2026Article
- Proteomic analysis of equine amniotic mesenchymal stromal cells and their extracellular vesicles: comparing their regenerative properties.Extracellular vesicles and circulating nucleic acids · 2026Article
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- USP14 Mediates Molecular Mechanisms Regulating Aortic Valve Stenosis Through Ubiquitination.Journal of cellular and molecular medicine · 2025Article
- Network toxicology and molecular docking elucidate the hepatotoxic and carcinogenic mechanisms of potassium sorbate validated by in vitro assays.Scientific reports · 2025Article
- Article
- Unveiling the Hub Genes Involved in Cadmium-Induced Hepatotoxicity.Biological trace element research · 2025Article
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- A Novel 167-Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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Abstract
Nonalcoholic fatty liver disease (NAFLD) begins with excessive triglyceride accumulation in the liver, and overly severe hepatic steatosis progresses to nonalcoholic steatohepatitis (NASH), which is characterized by lipid peroxidation, inflammation, and fibrosis. Ubiquitin-specific proteinase 14 (USP14) regulates inflammation, hepatocellular carcinoma and viral infection, but the effect of USP14 on NAFLD is unknown. The aim of this study was to reveal the role of USP14 in the progression of NAFLD and its underlying mechanism. We demonstrated that hepatic USP14 expression was significantly increased in NAFLD in both humans and mice. Hepatic USP14 overexpression exacerbated diet-induced hepatic steatosis, inflammation and fibrosis in mice, in contrast to the results of hepatic USP14 knockdown. Furthermore, palmitic/oleic acid-induced lipid peroxidation and inflammation in hepatocytes were markedly increased by USP14 overexpression but decreased by USP14 knockdown. Notably, in vivo or in vitro data show that USP14 promotes NAFLD progression in a cytochrome p4502E1 (CYP2E1)-dependent manner, which exacerbates hepatocyte oxidative stress, impairs the mitochondrial respiratory chain and inflammation by promoting CYP2E1 protein levels. Mechanistically, we demonstrated by immunoprecipitation and ubiquitination analysis that USP14 inhibits the degradation of heat shock protein 90 alpha family class A member 1 (HSP90AA1) by decreasing its lysine 48-linkage ubiquitination. Meanwhile, upregulation of HAP90AA1 protein promotes CYP2E1 protein accumulation. Collectively, our data indicate that an unknown USP14-HSP90AA1-CYP2E1 axis contributes to NAFLD progression, and we propose that inhibition of USP14 may be an effective strategy for NASH treatment.
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