ArticleThe Journal of biological chemistry2014
Interleukin-1 receptor-associated kinase-2 genetic variant rs708035 increases NF-κB activity through promoting TRAF6 ubiquitination.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- CD8+ T cells with high TGF‑β1 expression cause lymph node fibrosis following HIV infection.Molecular medicine reports · 2018Trial
- Toll-like receptors and their role in the pathogenesis of myasthenia gravis: a comprehensive review.Frontiers in immunology · 2025Review
- Pathways for macrophage uptake of cell-free circular RNAs.Molecular cell · 2024Article
- Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.Clinical and experimental medicine · 2023Review
- Article
- Review
- [Establishment of a congenital chloride diarrhea-associated SLC26A3 c.392C>G (p.P131R) polymorphism-expressing cell model and a preliminary analysis of its mechanism of action].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2019Article
- IRAK2 and TLR10 confer risk of Hashimoto's disease: a genetic association study based on the Han Chinese population.Journal of human genetics · 2019Article
- Functional characterization of SLC26A3 c.392C>G (p.P131R) mutation in intestinal barrier function using CRISPR/CAS9-created cell models.Cell & bioscience · 2019Article
- IRAK2 is associated with susceptibility to rheumatoid arthritis.Clinical rheumatology · 2018Article
- A miRNA Host Response Signature Accurately Discriminates Acute Respiratory Infection Etiologies.Frontiers in microbiology · 2018Article
- Loss of TAB3 expression by shRNA exhibits suppressive bioactivity and increased chemical sensitivity of ovarian cancer cell lines via the NF-κB pathway.Cell proliferation · 2016Article
- Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation.Mediators of inflammation · 2016Article
- CHOP links endoplasmic reticulum stress to NF-κB activation in the pathogenesis of nonalcoholic steatohepatitis.Molecular biology of the cell · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The IL-1 receptor-associated kinases (IRAKs) are key regulators of Toll-like receptor (TLR)/IL-1 signaling, which are critical regulators of mammalian inflammation and innate immune response. Single nucleotide polymorphisms (SNPs) within the IRAK genes have been discovered recently. However, the functions of these IRAK SNPs remain largely unknown. Here, we found that the non-synonymous IRAK2 variant rs708035 (coding D431E) increases NF-κB activity and leads to more expression of NF-κB-dependent proinflammatory cytokines compared with IRAK2 wild type. Moreover, when IRAK2 knockdown cells reconstituted with siRNA-resistant WT-IRAK2 or D431E-IRAK2 were infected with influenza virus, a more obvious induction of IL-6 and a stronger anti-apoptosis effect were observed in D431E-IRAK2 expressing cells. Notably, we also found that the levels of proinflammatory cytokine-IL-6 were indeed higher in people carrying D431E-IRAK2 than those carrying WT-IRAK2. Further study demonstrated that elevated NF-κB activation mediated by the IRAK2 variant was due to increased TRAF6 ubiquitination and faster IκBα degradation. Our study provides important insight of IRAK2 SNP in the regulation of NF-κB activation and indicates that IRAK2 rs708035 might be associated with human diseases caused by hyper-activation of NF-κB.
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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.