ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Ubiquitination of RORγt at Lysine 446 Limits Th17 Differentiation by Controlling Coactivator Recruitment.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Enhanced HIF-1α cooperation by a human RORγt mutant potentiates Th17 pathogenicity.Cell reports · 2026Article
- TDRD3, a Tudor domain-containing protein, regulatesScience advances · 2026Article
- Selective disruption of RORγt-CBFβ interaction by IMU-935 prevents RORγt-dependent Th17 autoimmunity but not thymocyte development.The Journal of clinical investigation · 2026Article
- Review
- USP15 Facilitates Colorectal Cancer Immune Evasion through SMYD3/CCL2-Dependent Myeloid-Derived Suppressor Cell Recruitment.Cancer immunology research · 2025Article
- N-glycosylated LTβR increases the Th17/Treg cell ratio in liver cancer by blocking RORC ubiquitination and FOXP3 transcription.Cell death & disease · 2025Article
- Gastric mucosal proteomic analysis reveals the role of the TGF-Frontiers in microbiology · 2025Article
- Fine-tuning immunity: ubiquitin-dependent regulation of interleukin-17A expression by Th17 cells.Frontiers in immunology · 2025Review
- Deubiquitinases and Cancer.Journal of pharmacy & bioallied sciences · 2024Review
- Ubiquitin Signaling in the Immune System.Advances in experimental medicine and biology · 2024Review
- USP28 protects development of inflammation in mouse intestine by regulating STAT5 phosphorylation and IL22 production in T lymphocytes.Frontiers in immunology · 2024Article
- Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases.Journal of pharmaceutical analysis · 2023Review
- USP1-regulated reciprocal differentiation of Th17 cells and Treg cells by deubiquitinating and stabilizing TAZ.Cellular & molecular immunology · 2023Article
- Article
- Deubiquitylating enzymes: potential target in autoimmune diseases.Inflammopharmacology · 2021Review
- RORγt protein modifications and IL-17-mediated inflammation.Trends in immunology · 2021Review
- Deubiquitinating enzymes (DUBs): DoUBle-edged swords in CNS autoimmunity.Journal of neuroinflammation · 2020Review
- (Inverse) Agonists of Retinoic Acid-Related Orphan Receptor γ: Regulation of Immune Responses, Inflammation, and Autoimmune Disease.Annual review of pharmacology and toxicology · 2020Review
- Deubiquitinating Enzyme: A Potential Secondary Checkpoint of Cancer Immunity.Frontiers in oncology · 2020Review
- Hectd3 promotes pathogenic Th17 lineage through Stat3 activation and Malt1 signaling in neuroinflammation.Nature communications · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The transcription factor retinoid acid-related orphan receptor γ t (RORγt) directs the differentiation of Th17 cells. Th17 cells mediate pathological immune responses responsible for autoimmune diseases, including psoriasis and multiple sclerosis. Previous studies focused on RORγt target genes and their function in Th17 differentiation. In this study, we assessed posttranscriptional regulation of RORγt and identified a functional ubiquitination site, K446. Mutation of K446 to arginine to prevent ubiquitination greatly enhanced recruitment of steroid receptor coactivator 1 (SRC1), a coactivator critical for RORγt activity. Correspondingly, the K446 to arginine mutation potentiated Th17 differentiation. We also showed that ubiquitin-specific protease (USP)15 interacted with RORγt, removed ubiquitin from K446, and stimulated RORγt activity by enhancing coactivator SRC1 recruitment. Knockdown of USP15 or expression of inactive USP15 impaired Th17 differentiation, suggesting a positive role for USP15-mediated deubiquitination of RORγt in Th17 differentiation. Therefore, ubiquitination of K446 limits RORγt-mediated Th17 differentiation by inhibiting the recruitment of coactivator SRC1. Our study will inform the development of treatments that target RORγt ubiquitination pathways to limit Th17-mediated autoimmunity.
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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.