ArticleNature immunology2014
Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO.
Article in Nature immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
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- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- ELK1 inhibition alleviates amyloid pathology and memory decline by promoting the SYVN1-mediated ubiquitination and degradation of PS1 in Alzheimer's disease.Experimental & molecular medicine · 2025Article
- Involvement of the ubiquitin-proteasome system in the regulation of the tumor microenvironment and progression.Genes & diseases · 2025Review
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- Farnesyl pyrophosphate potentiates dendritic cell migration in autoimmunity through mitochondrial remodelling.Nature metabolism · 2024Article
- Ulcerative colitis: molecular insights and intervention therapy.Molecular biomedicine · 2024Review
- N6-methyladenosine in myeloid cells: a novel regulatory factor for inflammation-related diseases.Journal of physiology and biochemistry · 2024Review
- EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death.Nature communications · 2024Article
- IL-6 and diabetic kidney disease.Frontiers in immunology · 2024Review
- The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy.Frontiers in immunology · 2024Review
- Role of Ubiquitin Signaling in Modulating Dendritic Cell Function.Advances in experimental medicine and biology · 2024Review
- Identification of ROH Islands Conserved through Generations in Pigs Belonging to the Nero Lucano Breed.Genes · 2023Article
- The Role of Deubiquitinating Enzyme in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2022Review
- Elevated ubiquitination contributes to protective immunity against severe SARS-CoV-2 infection.Clinical and translational medicine · 2022Article
- Immune-regulating strategy against rheumatoid arthritis by inducing tolerogenic dendritic cells with modified zinc peroxide nanoparticles.Journal of nanobiotechnology · 2022Article
- Whole-genome sequence analysis reveals selection signatures for important economic traits in Xiang pigs.Scientific reports · 2022Article
- K27-linked ubiquitylation promotes p97 substrate processing and is essential for cell proliferation.The EMBO journal · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive activation of dendritic cells (DCs) leads to the development of autoimmune and inflammatory diseases, which has prompted a search for regulators of DC activation. Here we report that Rhbdd3, a member of the rhomboid family of proteases, suppressed the activation of DCs and production of interleukin 6 (IL-6) triggered by Toll-like receptors (TLRs). Rhbdd3-deficient mice spontaneously developed autoimmune diseases characterized by an increased abundance of the TH17 subset of helper T cells and decreased number of regulatory T cells due to the increase in IL-6 from DCs. Rhbdd3 directly bound to Lys27 (K27)-linked polyubiquitin chains on Lys302 of the modulator NEMO (IKKγ) via the ubiquitin-binding-association (UBA) domain in endosomes. Rhbdd3 further recruited the deubiquitinase A20 via K27-linked polyubiquitin chains on Lys268 to inhibit K63-linked polyubiquitination of NEMO and thus suppressed activation of the transcription factor NF-κB in DCs. Our data identify Rhbdd3 as a critical regulator of DC activation and indicate K27-linked polyubiquitination is a potent ubiquitin-linked pattern involved in the control of autoimmunity.
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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.