ArticleNature medicine2018
The deubiquitinating enzyme cylindromatosis mitigates 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 76 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Pooled it
- Contribution of p38 MAPK in liver fibrosis: An overview of mechanisms, signaling pathways, and therapeutic targets (Review).International journal of molecular medicine · 2026Review
- TRIM47, stabilized by YTHDF3-mediated m6A modification, promotes cardiac lipid accumulation and aggravates diabetic cardiomyopathy.Molecular metabolism · 2026Article
- Trim47 protects against hypoxic-ischaemic brain injury in neonatal rats by reducing brain microvascular endothelial inflammation and BBB disruption by interacting with ZO1.Acta pharmacologica Sinica · 2026Article
- Loss of CYLD on Chromosome 16q Impairs Homologous Recombination and Genomic Stability Through TIRR Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial Cell TRIM47 Triggers Blood-Brain Barrier Disruption via CYLD Ubiquitination Degradation in an Intracerebral Hemorrhage Model.Neuroscience bulletin · 2026Article
- Roles of the E3 Ubiquitin Ligase TRIM47 in Inflammation, Organ Injury, and Cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Cleavage-Resistant CYLD Protects Against Autoimmune Hepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Caspase-8-mediated CYLD cleavage boosts LPS-induced endotoxic shock.Cell death and differentiation · 2026Article
- Deubiquitinases in liver diseases: from mechanisms to targeted therapy.Science China. Life sciences · 2026Review
- 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
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Phenotypic analysis of mice with inactivation of the deubiquitinating enzyme CYLD in adipose tissue.Cell and tissue research · 2025Article
- Association of liver fibrosis-4 index with functional outcomes in chinese patients with acute ischemic stroke undergoing mechanical thrombectomy.Scientific reports · 2025Article
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- Mettl1 knockdown alleviates cardiac I/R injury in mice by inactivating the Mettl1-CYLD-P53 positive feedback loop.Acta pharmacologica Sinica · 2025Article
- The ubiquitin-proteasome system: A potential target for the MASLD.Acta pharmaceutica Sinica. B · 2025Review
- BRISC inactivation alleviates alcohol-induced liver injury in mice.Scientific reports · 2025Article
- TRIM47 promotes head and neck squamous cell carcinoma malignant progression by degrading XAF1 through ubiquitination.iScience · 2025Article
- Ablation of the deubiquitinating enzyme cylindromatosis (CYLD) augments STAT1-mediated M1 macrophage polarization and fostersFrontiers in immunology · 2025Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 2 institutions in 2 countries.
Funding
Abstract
Nonalcoholic steatohepatitis (NASH) is a common clinical condition that can lead to advanced liver diseases. Lack of effective pharmacotherapies for NASH is largely attributable to an incomplete understanding of its pathogenesis. The deubiquitinase cylindromatosis (CYLD) plays key roles in inflammation and cancer. Here we identified CYLD as a suppressor of NASH in mice and in monkeys. CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity. We observed that overexpression of Cyld in hepatocytes concomitantly inhibits lipid accumulation, insulin resistance, inflammation and fibrosis in mice with NASH induced in an experimental setting. Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK-p38 cascades. Notably, reconstitution of hepatic CYLD expression effectively reverses disease progression in mice with dietary or genetically induced NASH and in high-fat diet-fed monkeys predisposed to metabolic syndrome. Collectively, our findings demonstrate that CYLD mitigates NASH severity and identify the CYLD-TAK1 axis as a promising therapeutic target for management of the disease.
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Registered trials
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.