ArticleScientific reports2015
Natural small molecule FMHM inhibits lipopolysaccharide-induced inflammatory response by promoting TRAF6 degradation via K48-linked polyubiquitination.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- K29-Linked Ubiquitination of Transcription Regulators Controls Cell Proliferation in the Unfolded Protein Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis.Open medicine (Warsaw, Poland) · 2025Article
- TheInternational journal of molecular sciences · 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
- Mechanism by which TRAF6 Participates in the Immune Regulation of Autoimmune Diseases and Cancer.BioMed research international · 2020Review
- MiR-590-3p Attenuates Acute Kidney Injury by Inhibiting Tumor Necrosis Factor Receptor-Associated Factor 6 in Septic Mice.Inflammation · 2019Article
- USP4 positively regulates RLR-induced NF-κB activation by targeting TRAF6 for K48-linked deubiquitination and inhibits enterovirus 71 replication.Scientific reports · 2018Article
- Role of the NFκB-signaling pathway in cancer.OncoTargets and therapy · 2018Review
- DR5-Cbl-b/c-Cbl-TRAF2 complex inhibits TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells.Molecular oncology · 2017Article
- Highly Selective Activation of Heat Shock Protein 70 by Allosteric Regulation Provides an Insight into Efficient Neuroinflammation Inhibition.EBioMedicine · 2017Article
- Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization.British journal of pharmacology · 2017Article
- Inositol polyphosphate multikinase promotes Toll-like receptor-induced inflammation by stabilizing TRAF6.Science advances · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TNF receptor-associated factor 6 (TRAF6) is a key hub protein involved in Toll-like receptor-dependent inflammatory signaling pathway, and it recruits additional proteins to form multiprotein complexes capable of activating downstream NF-κB inflammatory signaling pathway. Ubiquitin-proteasome system (UPS) plays a crucial role in various protein degradations, such as TRAF6, leading to inhibitory effects on inflammatory response and immunologic function. However, whether ubiquitination-dependent TRAF6 degradation can be used as a novel anti-inflammatory drug target still remains to be explored. FMHM, a bioactive natural small molecule compound extracted from Chinese herbal medicine Radix Polygalae, suppressed acute inflammatory response by targeting ubiquitin protein and inducing UPS-dependent TRAF6 degradation mechanism. It was found that FMHM targeted ubiquitin protein via Lys48 site directly induced Lys48 residue-linked polyubiquitination. This promoted Lys48 residue-linked polyubiquitin chain formation on TRAF6, resulting in increased TRAF6 degradation via UPS and inactivation of downstream NF-κB inflammatory pathway. Consequently, FMHM down-regulated inflammatory mediator levels in circulation, protected multiple organs against inflammatory injury in vivo, and prolong the survival of endotoxemia mouse models. Therefore, FMHM can serve as a novel lead compound for the development of TRAF6 scavenging agent via ubiquitination-dependent mode, which represents a promising strategy for treating inflammatory diseases.
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