ArticleCell death and differentiation2020
OTULIN protects the liver against cell death, inflammation, fibrosis, and cancer.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 81 citations in OpenAlex.
- Pharmacological Potential of Selenoproteins in the Regulation of Oxidative Stress in Liver Diseases.Pharmaceutics · 2026Review
- M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress.Cell death and differentiation · 2026Article
- Article
- Effect of Hydroxytyrosol on OTULIN Levels in Testıcular Tıssue in Experımental Dıabetes Model Induced wıth Streptozotocin.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- OTU deubiquitinases as immune-circuit editors: from human immunopathology to therapeutic prioritization.Frontiers in immunology · 2026Review
- OTULIN: a master regulator of linear ubiquitin homeostasis in immune signaling, inflammation, and disease.Frontiers in immunology · 2026Review
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Review
- Immunometabolic Targets in CD8Liver cancer · 2025Review
- The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025Review
- Linear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.Autophagy · 2025Article
- FAM105B Promotes Hepatocellular Carcinoma Progression and Metastasis by Activating the PI3K/AKT/MTOR Signaling Pathway and Inducing Epithelial-Mesenchymal Transition.Journal of hepatocellular carcinoma · 2025Article
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Dissecting the dual role of OTU family proteins in tumor progression and immune escape.Frontiers in immunology · 2025Review
- OTULIN confers cisplatin resistance in osteosarcoma by mediating GPX4 protein homeostasis to evade the mitochondrial apoptotic pathway.Journal of experimental & clinical cancer research : CR · 2024Article
- Review
- OTULIN Can Improve Spinal Cord Injury by the NF-κB and Wnt/β-Catenin Signaling Pathways.Molecular neurobiology · 2024Review
- LUBAC enables tumor-promoting LTβ receptor signaling by activating canonical NF-κB.Cell death and differentiation · 2024Article
- OTULIN's influence on neuroinflammation and pain modulation in trigeminal neuralgia.CNS neuroscience & therapeutics · 2024Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Methionine-1 (M1)-linked polyubiquitin chains conjugated by the linear ubiquitin chain assembly complex (LUBAC) control NF-κB activation, immune homoeostasis, and prevents tumour necrosis factor (TNF)-induced cell death. The deubiquitinase OTULIN negatively regulates M1-linked polyubiquitin signalling by removing the chains conjugated by LUBAC, and OTULIN deficiency causes OTULIN-related autoinflammatory syndrome (ORAS) in humans. However, the cellular pathways and physiological functions controlled by OTULIN remain poorly understood. Here, we show that OTULIN prevents development of liver disease in mice and humans. In an ORAS patient, OTULIN deficiency caused spontaneous and progressive steatotic liver disease at 10-13 months of age. Similarly, liver-specific deletion of OTULIN in mice leads to neonatally onset steatosis and hepatitis, akin to the ORAS patient. OTULIN deficiency triggers metabolic alterations, apoptosis, and inflammation in the liver. In mice, steatosis progresses to steatohepatitis, fibrosis and pre-malignant tumour formation by 8 weeks of age, and by the age of 7-12 months the phenotype has advanced to malignant hepatocellular carcinoma. Surprisingly, the pathology in OTULIN-deficient livers is independent of TNFR1 signalling. Instead, we find that steatohepatitis in OTULIN-deficient livers is associated with aberrant mTOR activation, and inhibition of mTOR by rapamycin administration significantly reduces the liver pathology. Collectively, our results reveal that OTULIN is critical for maintaining liver homoeostasis and suggest that M1-linked polyubiquitin chains may play a role in regulation of mTOR signalling and metabolism in the liver.
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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.