TRAF6 antibody - middle region (ARP30226_P050)
- Known as:
- TRAF6 (anti-) - middle region (ARP30226_P050)
- Catalog number:
- arp30226_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- TRAF6 antibody - middle region (ARP30226_P050)
Related genes to: TRAF6 antibody - middle region (ARP30226_P050)
- Gene:
- TRAF6 NIH gene
- Name:
- TNF receptor associated factor 6
- Previous symbol:
- -
- Synonyms:
- RNF85
- Chromosome:
- 11p12
- Locus Type:
- gene with protein product
- Date approved:
- 1997-06-12
- Date modifiied:
- 2015-11-20
Related products to: TRAF6 antibody - middle region (ARP30226_P050)
Related articles to: TRAF6 antibody - middle region (ARP30226_P050)
- Interleukin-17 (IL-17) family cytokines drive protective mucocutaneous immunity and, when dysregulated, a broad spectrum of inflammatory and autoimmune disease; almost all IL-17 receptor signaling converges on a single cytoplasmic adaptor, TRAF3IP2 (Act1/CIKS). This 574-amino-acid protein and U-box E3 ubiquitin ligase couples the IL-17 receptor to NF-κB and mitogen-activated protein kinase activation and also integrates non-IL-17 inputs through TRAF6, TRAF2/TRAF5, and TRAF3. Human germline variation in TRAF3IP2 offers a natural dissection of this adaptor along its signaling modules. Common coding variants that weaken TRAF6 recruitment, mainly rs33980500 (p.Asp19Asn), increase susceptibility to psoriasis and psoriatic arthritis, whereas rare biallelic variants that abolish SEFIR-mediated IL-17 receptor coupling cause chronic mucocutaneous candidiasis; an intermediate SEFIR lesion produces discoid lupus erythematosus. Additional associations span systemic lupus erythematosus, inflammatory bowel disease, cardiovascular disease, and malignancy. Interpreting these alleles has been limited by the absence of a variant catalogue anchored to a single protein reference and by a +9-residue offset between the 574- and 565-amino-acid isoforms that has propagated numbering errors across the literature. Here we assemble a reference-aligned atlas of 17 functionally or clinically annotated TRAF3IP2 variants on the 574-amino-acid sequence (NP_671733.2) and map each to the signaling interaction it perturbs. The resulting domain-to-phenotype framework, advanced as hypothesis-generating rather than deterministic, organizes variant effects along the IL-17 signaling axis, distinguishing TRAF-recruitment perturbation from receptor-coupling failure, and identifies the adaptor surfaces whose selective pharmacologic disruption could attenuate IL-17-driven inflammation in cardiovascular and oncologic disease while sparing antifungal immunity. - Source: PubMed
Publication date: 2026/08/18
Alt Eckhard UIzadpanah Reza - Pediatric pneumonia remains a leading cause of childhood mortality worldwide, and lipopolysaccharide (LPS)-induced pulmonary cell injury plays a critical role in its pathogenesis. Atractylenolide I (ATL-1), a sesquiterpene lactone derived from Atractylodes macrocephala Koidz., possesses well-documented anti-inflammatory properties. However, its protective effects against LPS-induced lung cell injury remain unclear. In this study, WI-38 human embryonic lung fibroblasts and BEAS-2B human bronchial epithelial cells were stimulated with LPS to establish complementary in vitro models of pulmonary cell injury relevant to pediatric pneumonia. ATL-1 dose-dependently restored cell viability, inhibited apoptosis, and suppressed the production of IL-6, TNF-α, and IL-1β. Mechanistically, ATL-1 upregulated both Mcl-1 and Survivin through distinct regulatory mechanisms. ATL-1 restored ERK signaling to upregulate the deubiquitinase USP9X, which inhibited Mcl-1 ubiquitination and enhanced its protein stability. Meanwhile, ATL-1 restored Akt activity to promote Survivin expression at the transcriptional level. Knockdown of Mcl-1, Survivin, or USP9X abolished the protective effects of ATL-1. Similarly, pharmacological inhibition of ERK or Akt reversed ATL-1-mediated cytoprotection. Upstream, ATL-1 reduced MD2-TLR4 association and attenuated MD2/TLR4/MyD88/TRAF6/NF-κB signaling. CETSA and SPR analyses supported the interaction between ATL-1 and MD2. Time-course and NF-κB loss-of-function experiments further showed that suppression of sustained NF-κB signaling preceded and contributed to the restoration of ERK- and Akt-dependent pro-survival pathways. MD2 depletion mimicked and largely occluded the downstream effects of ATL-1. These findings demonstrate that ATL-1 alleviates LPS-induced cell injury and inflammatory responses through the coordinated restoration of the ERK/USP9X/Mcl-1 and Akt/Survivin axes. This study provides mechanistic insight into ATL-1's cytoprotective effects and supports further evaluation in additional models of pneumonia-associated lung injury. - Source: PubMed
Publication date: 2026/08/21
Xu JingleiLi FangQian XinWu Peini - To investigate the pathogen-associated molecular recognition characteristics and immune response of Toll-like receptor 22 (TLR22) in Micropterus salmoides, sequence characterization was performed, and its potential immune functions were further evaluated through tissue expression profiling, pathogen-associated stimulation response analysis, recombinant protein binding assays, and in vivo challenge experiments. The results showed that the open reading frame of TLR22 in M. salmoides was 2880 bp in length and encoded 959 amino acids. The deduced protein exhibited the typical structural features of teleost TLR22 and showed high sequence homology with TLR22 from other teleost species. TLR22 was expressed in all examined tissues, with relatively high expression levels in the head kidney and spleen. Stimulation with poly(I:C), lipopolysaccharide (LPS), and Aeromonas hydrophila significantly induced temporal changes in TLR22 expression in the head kidney, liver, and spleen. Recombinant TLR22 protein was able to bind multiple bacterial species and pathogen-associated molecular patterns, and displayed differential binding activities toward different ligands. In vivo challenge experiments showed that pretreatment with recombinant TLR22 protein enhanced the expression responses of immune-related genes, including TLR22, traf6, IL-6, IL-1β, and hepcidin, in relevant tissues following A. hydrophila infection. The TLR22-Ah group also exhibited a numerically higher final survival rate than the PBS-Ah and TrxA-Ah groups, although the pairwise differences were not statistically significant. Collectively, these results suggest that TLR22 in M. salmoides may participate in pathogen stimulus-induced innate immune responses and play important roles in pathogen recognition and immune regulation. This study provides a basis for further elucidating the immunological function of TLR22 in M. salmoides. - Source: PubMed
Publication date: 2026/08/20
Wang KeLu Ling YunLiu YuLiu ShaozhenWang WeiweiSong JingWang XianzongLiu Qing - Obesity constitutes a significant worldwide health challenge and a primary risk factor for cardiovascular diseases. Diacerein, an anti-inflammatory medication approved for osteoarthritis, is being studied as a potential modulator of inflammatory signaling. However, its role in obesity-associated cardiovascular injury remains incompletely understood. In the present study, computational docking and 300-ns MD simulations supported preferential, stable binding of diacerein to the TLR4 complex through a deep, hydrophobic, solvent-shielded pose, consistent with coordinated protein dynamics. Then, the cardioprotective effects of diacerein were examined in a high-fat diet (HFD)-induced obesity model. Male Sprague-Dawley rats were divided into three groups: normal control, HFD, and HFD combined with diacerein (50 mg/kg/day) for 10 weeks. Metabolic parameters, lipid profile, serum troponin I, and C-reactive protein (CRP) were evaluated. A histopathological examination of the heart and aorta was conducted, and the tissue levels of TLR4, MyD88, IRAK1, TRAF6, NF-κB, and downstream pro-inflammatory cytokines (IL-6 and TNF-α) were assessed. Inflammatory cell infiltration was evaluated using CD45 immunohistochemistry. The HFD led to insulin resistance, dyslipidemia, increased troponin I and CRP levels, and significant histological alterations in cardiac and aortic tissues, accompanied by the activation of the TLR4/NF-κB inflammatory pathway and enhanced inflammatory cell infiltration. Diacerein treatment markedly alleviated metabolic abnormalities, diminished cardiac injury and systemic inflammation, improved histological features, and reduced tissue protein levels of the TLR4/NF-κB pathway and pro-inflammatory cytokines. In conclusion, diacerein provides marked protection against obesity-induced cardiovascular injury, at least partially, by inhibiting the TLR4/NF-κB inflammatory pathway, supporting its potential as a therapeutic strategy for obesity-related cardiovascular complications. - Source: PubMed
Publication date: 2026/08/20
Alatawi Shahad MAljadrawi Sara FAlanazi Layan SAljohani Yara AElsherbiny NehalAbo-Dya Nader EQushawy MonaAhmed Salwa Fares - Toll-like receptor (TLR) signaling must be activated rapidly and then terminated to support host defense without sustained inflammation. We developed a rule-based model of mouse macrophage TLR4 signaling at the molecular-interaction level using measured protein copy numbers, RNA-seq-based abundance estimates, literature- and structure-informed reaction rates, and 979 dynamic experimental constraints. The trained model reproduced much of the TLR4-induced NF-κB and MAP kinase response but consistently failed to capture deactivation of MyD88, TRAF6-associated species, and IKKα/β. The recurrent model failure conveyed important biological information, localizing missing regulation to the proximal MyD88-IRAK-TRAF6 module and guiding experimental evaluation of IKKε and its scaffold TANK. Loss of IKKε enhanced transcriptional, cytokine, MAP kinase, and NF-κB responses to MyD88-specific TLR ligands. TANK deficiency produced a similar cellular phenotype and abolished stimulus-induced IKKε phosphorylation. Deficiency of either protein increased IRAK1 and TRAF6 ubiquitination without increasing MyD88 ubiquitination, placing the inhibitory checkpoint at or immediately downstream of the IRAK1-TRAF6 ubiquitin-signaling node. Overlapping but non-identical in vivo phenotypes further supported a shared regulatory axis with additional protein-specific functions. Our study presents a model-experiment discovery cycle where quantitative pathway discordance identifies missing biology and reveals a TANK-dependent IKKε checkpoint that restrains MyD88-driven inflammation. - Source: PubMed
Publication date: 2026/08/16
Manes Nathan PZhang FengkaiLin BinSun JingHassan Sergio AArmstrong Anthony AShao YutingCalzola Jessica MKaplan-Stafford Pauline RGottschalk Rachel AMarino Matthew JKim DoeunGermain Ronald NFraser Iain D CMeier-Schellersheim MartinNita-Lazar Aleksandra