ArticleProceedings of the National Academy of Sciences of the United States of America2015
Type I IFN induces protein ISGylation to enhance cytokine expression and augments colonic inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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Who cites it
35 citing papers in PubMed, 62 citations in OpenAlex.
- Understanding protein ISGylation, a multifaceted posttranslational modification.Cell chemical biology · 2026Review
- Spleen-targeted neoantigen mRNA vaccine induces ISG15Cell reports. Medicine · 2026Article
- Targeting the cGAS-STING Pathway: Modulating Inflammation, Oxidative Stress, and Autophagy for Novel Depression Therapies.Current neuropharmacology · 2026Review
- Mitochondrial checkpoint for interferon responses in macrophages.Exploration of targeted anti-tumor therapy · 2026Review
- Review
- Innate immune sensing and signaling: Co-opted for genome surveillance? Implications for tumorigenesis.DNA repair · 2025Review
- Predictive value of neutrophil-to-lymphocyte ratio combined with carcinoembryonic antigen in postoperative adjuvant chemotherapy after gastric cancer surgery.World journal of gastrointestinal oncology · 2025Article
- A new severe congenital neutropenia syndrome associated with autosomal recessive COPZ1 mutations.Blood · 2025Article
- ISGylation: is our genome yearning for such a modification?Acta biochimica et biophysica Sinica · 2025Review
- The dichotomic role of cytokines in aging.Biogerontology · 2024Review
- The cGAS-STING pathway in viral infections: a promising link between inflammation, oxidative stress and autophagy.Frontiers in immunology · 2024Review
- Dynamic RBM47 ISGylation confers broad immunoprotection against lung injury and tumorigenesis via TSC22D3 downregulation.Cell death discovery · 2023Article
- ISG15 suppresses ovulation and female fertility by ISGylating ADAMTS1.Cell & bioscience · 2023Article
- The Functional Roles of ISG15/ISGylation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- Dapagliflozin alleviates renal inflammation and protects against diabetic kidney diseases, both dependent and independent of blood glucose levels.Frontiers in immunology · 2023Article
- Systems crosstalk between antiviral response and cancerous pathways via extracellular vesicles in HIV-1-associated colorectal cancer.Computational and structural biotechnology journal · 2023Article
- The diverse repertoire of ISG15: more intricate than initially thought.Experimental & molecular medicine · 2022Review
- ISGylation is increased in the peripheral blood mononuclear cells derived from symptomatic COVID-19 patients.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Use of integrated metabolomics, transcriptomics, and signal protein profile to characterize the effector function and associated metabotype of polarized macrophage phenotypes.Journal of leukocyte biology · 2022Article
- ISG15 and ISGylation in Human Diseases.Cells · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Type I IFNs have broad activity in tissue inflammation and malignant progression that depends on the expression of IFN-stimulated genes (ISGs). ISG15, one such ISG, can form covalent conjugates to many cellular proteins, a process termed "protein ISGylation." Although type I IFNs are involved in multiple inflammatory disorders, the role of protein ISGylation during inflammation has not been evaluated. Here we report that protein ISGylation exacerbates intestinal inflammation and colitis-associated colon cancer in mice. Mechanistically, we demonstrate that protein ISGylation negatively regulates the ubiquitin-proteasome system, leading to increased production of IFN-induced reactive oxygen species (ROS). The increased cellular ROS then enhances LPS-induced activation of p38 MAP kinase and the expression of inflammation-related cytokines in macrophages. Thus our studies reveal a regulatory role for protein ISGylation in colonic inflammation and its related malignant progression, indicating that targeting ubiquitin-activating enzyme E1 homolog has therapeutic potential in treating inflammatory diseases.
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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.