ArticleNature medicine2018
The deubiquitinating enzyme TNFAIP3 mediates inactivation of hepatic ASK1 and ameliorates nonalcoholic steatohepatitis.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 183 citations in OpenAlex.
- A20 Inhibits IFN-γ Signaling in Hepatocellular Carcinoma Cells by Binding to STAT1, Compromising Anti-Tumor Immunity.Cancer science · 2026Article
- All-trans retinoic acid suppresses systemic inflammation induced by severe fever with thrombocytopenia syndrome virus in mice.Nature microbiology · 2026Article
- NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- USP13 promotes hepatic stellate cells activation and aggravates liver fibrosis through deubiquitinating SMAD3.Hepatology international · 2026Article
- ALKBH5 facilitates Srgn stability via m6A demethylation to disrupt blood-testis barrier integrity in the high-fat diet mice.Cellular and molecular life sciences : CMLS · 2026Article
- Tao-Hong-Si-Wu-Tang protects against methionine- and choline-deficient diet-induced hepatic steatosis in rats and is associated with inhibition of oxidative stress, inflammation, apoptosis, and pyroptosis.Frontiers in immunology · 2026Article
- The NLRP3 inflammasome in metabolic dysfunction-associated steatotic liver disease: role and advances in therapeutic targeting.Frontiers in immunology · 2026Review
- Protein deglycase DJ-1 deficiency aggravates acute viral myocarditis by promoting apoptosis via reducing Dusp1 expression.Cell death & disease · 2025Article
- Aberrant alternative splicing in alcoholic hepatitis: regulatory roles of RBPs and sQTLs.BMC gastroenterology · 2025Article
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death.Cell death discovery · 2025Review
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- The ubiquitin-proteasome system: A potential target for the MASLD.Acta pharmaceutica Sinica. B · 2025Review
- Immunometabolism of Liver Xenotransplantation and Prospective Solutions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- At the Crossroads of Health and Disease: Consequences of Fat in the Liver.Annual review of physiology · 2025Review
- Deubiquitinase JOSD1 tempers hepatic proteotoxicity.Cell death discovery · 2024Article
- Article
- From NAFLD to NASH: Understanding the spectrum of non-alcoholic liver diseases and their consequences.Heliyon · 2024Review
- Targeting hepatic ceruloplasmin mitigates nonalcoholic steatohepatitis by modulating bile acid metabolism.Journal of molecular cell biology · 2024Article
- Pharmacological Activation of AMPK Prevents Drp1-mediated Mitochondrial Fission and Alleviates Hepatic SteatosisCurrent molecular medicine · 2024Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of apoptosis signal-regulating kinase 1 (ASK1) in hepatocytes is a key process in the progression of nonalcoholic steatohepatitis (NASH) and a promising target for treatment of the condition. However, the mechanism underlying ASK1 activation is still unclear, and thus the endogenous regulators of this kinase remain open to be exploited as potential therapeutic targets. In screening for proteins that interact with ASK1 in the context of NASH, we identified the deubiquitinase tumor necrosis factor alpha-induced protein 3 (TNFAIP3) as a key endogenous suppressor of ASK1 activation, and we found that TNFAIP3 directly interacts with and deubiquitinates ASK1 in hepatocytes. Hepatocyte-specific ablation of Tnfaip3 exacerbated nonalcoholic fatty liver disease- and NASH-related phenotypes in mice, including glucose metabolism disorders, lipid accumulation and enhanced inflammation, in an ASK1-dependent manner. In contrast, transgenic or adeno-associated virus-mediated TNFAIP3 gene delivery in the liver in both mouse and nonhuman primate models of NASH substantially blocked the onset and progression of the disease. These results implicate TNFAIP3 as a functionally important endogenous suppressor of ASK1 hyperactivation in the pathogenesis of NASH and identify it as a potential new molecular target for NASH therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.