ArticleCell death & disease2012
USP18 is a key regulator of the interferon-driven gene network modulating pancreatic beta cell inflammation and apoptosis.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Molecular Footprints of the Immune Assault on Pancreatic Beta Cells in Type 1 Diabetes.Frontiers in endocrinology · 2020Pooled it
- Transcriptome meta-analysis reveals a dysregulation in extra cellular matrix and cell junction associated gene signatures during Dengue virus infection.Scientific reports · 2016Pooled it
- Subtype-specific functions of basal IFNλs.Journal of virology · 2026Review
- From bats to humans: uncoveringbioRxiv : the preprint server for biology · 2026Article
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Roles of ubiquitin-specific proteases in inflammatory diseases.Frontiers in immunology · 2024Review
- Effect of Rotavirus Infection and 2'-Fucosyllactose Administration on Rat Intestinal Gene Expression.Nutrients · 2023Article
- Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders.International journal of molecular sciences · 2023Review
- Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β cells.Science advances · 2022Article
- Deubiquitinases: Modulators of Different Types of Regulated Cell Death.International journal of molecular sciences · 2021Review
- Determinants of Ligand Specificity and Functional Plasticity in Type I Interferon Signaling.Frontiers in immunology · 2021Article
- Relationship Between Ubiquitin-Specific Peptidase 18 and Hypertension in Polish Adult Male Subjects: A Cross-Sectional Pilot Study.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- The T1D-associated lncRNAProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Genetic perturbation of IFN-α transcriptional modulators in human endothelial cells uncovers pivotal regulators of angiogenesis.Computational and structural biotechnology journal · 2020Article
- Hepatitis C Virus Infection: Host⁻Virus Interaction and Mechanisms of Viral Persistence.Cells · 2019Review
- DEXI, a candidate gene for type 1 diabetes, modulates rat and human pancreatic beta cell inflammation via regulation of the type I IFN/STAT signalling pathway.Diabetologia · 2019Article
- Comparison of ISG15, IL28B and USP18 mRNA levels in peripheral blood mononuclear cells of chronic hepatitis B virus infected patients and healthy individuals.Gastroenterology and hepatology from bed to bench · 2019Article
- The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019Review
- NaJournal of the Endocrine Society · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes (T1D) is an autoimmune disease targeting pancreatic beta cells. Genome-wide association studies and gene expression analysis identified interferon (IFN)-driven gene networks as crucial pathways in the pathogenesis of T1D. IFNs are linked to the response to viral infections and might contribute to the initiation of the autoimmune process in T1D. We presently analyzed the role of ubiquitin-specific peptidase 18 (USP18), an interferon-stimulated gene 15-specific protease, on IFN-induced pancreatic beta cell inflammation and apoptosis. Our findings indicate that USP18 inhibition induces inflammation by increasing the STAT signaling and exacerbates IFN-induced beta cell apoptosis by the mitochondrial pathway of cell death. USP18 regulates activation of three BH3-only proteins, namely, DP5, Bim and PUMA in pancreatic beta cells, suggesting a direct link between regulators of the type I IFN signaling pathway and members of the BCL-2 family. USP18 depletion increases the expression of the T1D candidate gene MDA5, leading to an upregulation of double-stranded RNA-induced chemokine production. These data suggest a cross talk between the type I IFN signaling pathway and a candidate gene for T1D to increase pro-inflammatory responses in beta cells. The present study shows that USP18 is a key regulator of IFN signaling in beta cells and underlines the importance of this pathway in beta cell inflammation and death.
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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.