Ask about this productRelated genes to: TRAFD1 antibody
- Gene:
- TRAFD1 NIH gene
- Name:
- TRAF-type zinc finger domain containing 1
- Previous symbol:
- -
- Synonyms:
- FLN29
- Chromosome:
- 12q24.13
- Locus Type:
- gene with protein product
- Date approved:
- 2005-05-30
- Date modifiied:
- 2019-03-20
Related products to: TRAFD1 antibody
Related articles to: TRAFD1 antibody
- Excessive macrophage-mediated inflammation following myocardial infarction (MI) exacerbates infarct expansion and impairs cardiac repair; however, the regulatory mechanisms remain poorly understood. Here, it is reported that ubiquitin-specific peptidase 9 X-linked (USP9X) was significantly downregulated in macrophages during early post-MI inflammation. Macrophage-specific deficiency of USP9X enhanced expression of pro-inflammatory genes, thereby impeding cardiac functional recovery. Mechanistically, USP9X deubiquitinated and stabilized tumor necrosis factor receptor-associated factor (TRAF)-type zinc finger domain containing 1 (TRAFD1), a negative regulator of Toll-like receptor (TLR) signaling, thereby restraining inflammatory responses. Moreover, inflammatory stimuli triggered acetylation of USP9X at K2414, exposing a latent KFERQ motif that promoted its recognition by the molecular chaperone heat shock cognate protein 70 (HSC70) and facilitated subsequent lysosomal degradation via chaperone-mediated autophagy (CMA). Consistently, both genetic inhibition of HSC70 and pharmacological blockade of lysosomal degradation prevented USP9X degradation following inflammatory stimulation. Furthermore, a cell-penetrating peptide mimicking the KFERQ sequence of USP9X that blocked its interaction with HSC70 and the subsequent CMA-mediated degradation, thereby promoting inflammation resolution and cardiac repair post-MI. Collectively, these findings establish the USP9X-TRAFD1 axis and its CMA-mediated degradation as critical checkpoints in post-MI inflammation, highlighting USP9X stabilization as a therapeutic strategy for ischemic heart disease. - Source: PubMed
Publication date: 2026/01/28
Wang BiqingCai XianghengLi MengqiLiu XueXue JunhuiLiu YeAi DingHu Xinyang - Osteoarthritis (OA) is the most prevalent joint disease among the middle-aged and elderly individuals, primarily characterized by synovitis and cartilage damage. Although non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to manage OA, they fail to fundamentally prevent or alleviate cartilage damage and can cause severe gastrointestinal or cardiovascular side effects. Therefore, developing OA drugs that address both symptoms and underlying causes is of significant importance. Our study found that tigloside (TIG), a main metabolite derived from symbiotic actinomyces, could repolarize macrophages from pro-inflammatory M1 type to anti-inflammatory M2 type, suppress the release of multiple inflammatory factors and facilitate the secretion of the anti-inflammatory cytokine IL-10, thereby creating a favorable microenvironment for chondrocyte regeneration and extracellular matrix (ECM), and alleviating pain, synovitis and OA cartilage damage. Mechanistically, TIG competes with the signaling adaptor molecule Traf1 to bind at the middle region (aa 104-414) of Trafd1, disrupting the interaction between Trafd1 and Traf1. This disruption promotes the degradation of Trafd1 and Traf1 via proteasome-ubiquitination pathway, leading to a reduction in their protein levels. Consequently, the downregulation of Trafd1 further inhibits NF-κB signaling and M1 polarization while promoting STAT6 pathway and M2 polarization, resulting in the repolarization of macrophages from M1 to M2 type and the amelioration of OA. Importantly, these findings were further validated in human macrophages derived from OA patients. In summary, this study highlights the potential of TIG as a disease-modifying drug for OA, and identifies Trafd1 as a novel therapeutic target for OA treatment. - Source: PubMed
Publication date: 2025/11/04
Chen BoWang HuaYang YuehuaWang WenboZuo MinZhou JianghongTang SanquanZhai RuiruiLiu ShimeiAi YixiangGuo ZhikaiLiu Rangru - In this study, we tested whether our previously developed biomarker analysis could evaluate the bioactivity of SARS-Cov-2 mRNA vaccines, including their toxicity profiles. We also identified novel biomarkers that could be used to evaluate mRNA vaccine quality by analyzing global gene expression. We administered saline (SA), an influenza hemagglutinin (HA) vaccine, a toxic reference influenza vaccine (RE), and different amounts of an mRNA vaccine (Spikevax or COMIRNATY) to mice, either intraperitoneally or intramuscularly. Sixteen hours post-administration, we analyzed mouse body weight (BW), white blood cell (WBC) count, plasma cytokine levels, and biomarker gene expression in the lungs. Moreover, we performed a comprehensive gene expression analysis using DNA microarrays. BW and WBC count in the mRNA vaccine and RE groups significantly decreased compared with those in the HA group. BW and WBC count between the mRNA vaccine and RE groups did not significantly differ. In contrast, analysis of the expression levels of 15 biomarker genes revealed that 14 of the 15 biomarkers in the Spikevax group and all biomarkers in the COMIRNATY group were significantly upregulated compared with those in the HA group. The expression levels of some biomarkers (Psme1, Trafd1, Lgals9, Mx2) were significantly higher in the mRNA groups than those in the RE group. Furthermore, the mRNA vaccine groups exhibited significantly higher production of inflammatory cytokines than did the HA and RE groups. Global gene expression analysis revealed the gene signature following mRNA vaccination and confirmed that most of our biomarkers were present in the set of genes that were upregulated in the mRNA vaccine groups. In addition, we identified novel genes with significantly increased mRNA expression levels. Our results suggest that this biomarker-based evaluation system is highly sensitive to mRNA vaccine bioactivity and is useful for assessing vaccine safety in the quality control of mRNA vaccines. - Source: PubMed
Publication date: 2025/10/04
Hiraga KouMomose HarukaKuribayashi WakakoUemura MamiSakuragi SayuriNojima KiyokoIshii MiekoImai KeikoMaeyama Jun-IchiNakano KazumiSeki YoheiTezuka KentaKuramitsu MadokaMizukami Takuo - Lung cancer and cardiovascular disease pose persistent threats to human health, despite advancements in targeted therapy, percutaneous coronary intervention, and drug treatments. Challenges such as side effects, drug resistance, hospitalization rates, and mortality remain high. These diseases are closely linked, sharing common risk factors and intricately influencing each other. This study aims to investigate the interplay between lung disease and cardiovascular disease by examining changes in cardiac metabolites and protein expression using spatial metabolomics and 4D-DIA quantitative proteomics approaches in the setting of lung cancer. Nude mice were selected and A549 cells were injected axillary and metabolomics was used to observe the alterations in cardiac metabolism in the setting of lung cancer in nude mice.The findings reveal well-defined tumor structures. Further, spatial mass spectrometry imaging analysis demonstrates distinct metabolite distributions across cardiac regions, indicating significant differences between control and model groups. Through spatial metabolomics and proteomics analyses, key differential metabolites such as Gln-His-Val-Glu, LysoPC 22:6, and LPC (20:2/0:0), primarily amino acids, and glycerophospholipids, as well as differential proteins including Mknk1, Trafd1, Dab2ip, Tab1, Ripk3, G3PDH, and Mapk15, are identified. These results underscore the crucial role of these factors in cardiovascular injury. This study elucidates the intricate link between lung cancer and cardiovascular disease and identifies altered metabolites and proteins in the heart within a lung cancer environment. These insights are pivotal for informing future treatments and interventions for both diseases. - Source: PubMed
Publication date: 2025/04/28
Bai TingtingWan QuanYue ChangchengWang JingjingDeng ShichaoShen XueyingWang HongqingHuang LiyanWang Dong - Circulating cytokines orchestrate immune reactions and are promising drug targets for immune-mediated and inflammatory diseases. Exploring the genetic architecture of circulating cytokine levels could yield key insights into causal mediators of human disease. Here, we performed genome-wide association studies (GWAS) for 40 circulating cytokines in meta-analyses of 74,783 individuals. We detected 359 significant associations between cytokine levels and variants in 169 independent loci, including 150 trans- and 19 cis-acting loci. Integration with transcriptomic data point to key regulatory mechanisms, such as the buffering function of the Atypical Chemokine Receptor 1 (ACKR1) acting as scavenger for multiple chemokines and the role of tumor necrosis factor receptor-associated factor 1 (TRAFD1) in modulating the cytokine storm triggered by TNF signaling. Applying Mendelian randomization (MR), we detected a network of complex cytokine interconnections with TNF-b, VEGF, and IL-1ra exhibiting pleiotropic downstream effects on multiple cytokines. Drug target cis-MR using 2 independent proteomics datasets paired with colocalization revealed G-CSF/CSF-3 and CXCL9/MIG as potential causal mediators of asthma and Crohn's disease, respectively, but also a potentially protective role of TNF-b in multiple sclerosis. Our results provide an overview of the genetic architecture of circulating cytokines and could guide the development of targeted immunotherapies. - Source: PubMed
Publication date: 2025/01/10
Konieczny Marek JOmarov MuradZhang LanyueMalik RainerRichardson Tom GBaumeister Sebastian-EdgarBernhagen JürgenDichgans MartinGeorgakis Marios K