ArticleMolecular and cellular biology2008
Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.
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Who cites it
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.
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- Review
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling.Frontiers in immunology · 2026Review
- KBTBD11 loss promotes AKT hyperactivation and therapeutic vulnerability in prostate cancer.Oncogene · 2025Article
- Regulation of Neuroinflammation by Microglial DUBA-IRAK1-IKKβ Signaling Loop.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- The ubiquitin ligase Pellino1 targets STAT3 to regulate macrophage-mediated inflammation and tumor development.Nature communications · 2025Article
- A ubiquitin-specific, proximity-based labeling approach for the identification of ubiquitin ligase substrates.Science advances · 2024Article
- BLK positively regulates TLR/IL-1R signaling by catalyzing TOLLIP phosphorylation.The Journal of cell biology · 2024Article
- Tumor Necrosis Factor Receptor-Associated Factor 6 and Human Cancer: A Systematic Review of Mechanistic Insights, Functional Roles, and Therapeutic Potential.Journal of Cancer · 2024Review
- A noncanonical IRAK4-IRAK1 pathway counters DNA damage-induced apoptosis independently of TLR/IL-1R signaling.Science signaling · 2023Article
- MiR-146a-5p deficiency in extracellular vesicles of glioma-associated macrophages promotes epithelial-mesenchymal transition through the NF-κB signaling pathway.Cell death discovery · 2023Article
- Regulation of innate immune signaling by IRAK proteins.Frontiers in immunology · 2023Review
- Identification of ester-linked ubiquitylation sites during TLR7 signalling increases the number of inter-ubiquitin linkages from 8 to 12.The Biochemical journal · 2022Article
- Kruppel-like factor 13 inhibits cell proliferation of gastric cancer by inducing autophagic degradation of β-catenin.Discover oncology · 2022Article
- The Railmap of Type I Interferon Induction: Subcellular Network Plan and How Viruses Can Change Tracks.Cells · 2022Review
- The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways.Cell reports · 2022Article
- Reciprocal regulation of IL-33 receptor-mediated inflammatory response and pulmonary fibrosis by TRAF6 and USP38.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
71 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Stimulation through the interleukin-1 receptor (IL-1R) and some Toll-like receptors (TLRs) induces ubiquitination of TRAF6 and IRAK-1, signaling components required for NF-kappaB and mitogen-activated protein kinase activation. Here we show that although TRAF6 and IRAK-1 acquired Lys63 (K63)-linked polyubiquitin chains upon IL-1 stimulation, only ubiquitinated IRAK-1 bound NEMO, the regulatory subunit of IkappaB kinase (IKK). The sites of IRAK-1 ubiquitination were mapped to Lys134 and Lys180, and arginine substitution of these residues impaired IL-1R/TLR-mediated IRAK-1 ubiquitination, NEMO binding, and NF-kappaB activation. K63-linked ubiquitination of IRAK-1 required enzymatically active TRAF6, indicating that it is the physiologically relevant E3. Thus, K63-linked polyubiquitination of proximal signaling proteins is a common mechanism used by diverse innate immune receptors for recruiting IKK and activating NF-kappaB.
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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.