Phospho STAT_1 (Tyr727) pAb
- Known as:
- Phospho STAT_1 (Tyr727) pAb
- Catalog number:
- ASAKAP-TF021D
- Product Quantity:
- 50 µg
- Category:
- -
- Supplier:
- Other suppliers
- Gene target:
- Phospho STAT_1 (Tyr727) pAb
Related genes to: Phospho STAT_1 (Tyr727) pAb
- Gene:
- STAT1 NIH gene
- Name:
- signal transducer and activator of transcription 1
- Previous symbol:
- -
- Synonyms:
- STAT91, ISGF-3
- Chromosome:
- 2q32.2
- Locus Type:
- gene with protein product
- Date approved:
- 1995-11-08
- Date modifiied:
- 2019-04-23
- Gene:
- STAT2 NIH gene
- Name:
- signal transducer and activator of transcription 2
- Previous symbol:
- -
- Synonyms:
- STAT113
- Chromosome:
- 12q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1995-11-08
- Date modifiied:
- 2019-04-23
Related products to: Phospho STAT_1 (Tyr727) pAb
Related articles to: Phospho STAT_1 (Tyr727) pAb
- Inflammatory bowel disease (IBD) is characterized by unresolved mucosal inflammation driven mainly by TNFα and/or IFNγ. While anti-TNFα biologics are a clinical mainstay, therapeutic resistance remains a significant hurdle. The molecular mechanisms that sustain inflammation in anti-TNFα non-responders are not fully understood. In human colon biopsies, we identified significant upregulation of the deubiquitinase OTUD5 in non-responders compared to responders, suggesting its involvement in therapy resistance. Using an intestinal epithelial cell (IEC)-specific Otud5 knockout mouse model, we show that Otud5 deficiency significantly alleviated the IFNγ-dependent colitis induced by dextran sulfate sodium (DSS), as evidenced by reduced weight loss and diminished infiltration of Ly6C inflammatory monocytes. Mechanistically, IFNγ induces OTUD5 expression through a non-transcriptional mechanism; in turn, OTUD5 stabilizes STAT1 and STAT2 by preventing their ubiquitination and subsequent degradation. This sustains IFNγ-ISGF3 signaling, which directly drives the expression of CCL8, a critical chemokine for monocyte recruitment. Targeting this pathway with a newly identified small-molecule inhibitor, CT1170, which exhibits potent activity against OTUD5, blocked the IFNγ-ISGF3-CCL8 axis, halted colitis progression, and suppressed colitis-elicited tumorigenesis. These findings were validated in human IBD organoids, where CT1170 effectively disrupted IFNγ-driven inflammatory signaling. - Source: PubMed
Publication date: 2026/08/13
Guan HuiyuanCai ChangzhouWang JieweiLiu ZhaoxuePeng JinBai XupengWu LingzhiJiang KunZhen XinghuaYu ChaohuiZhang PuminShen Zhe - Rheumatoid arthritis (RA) is driven in part by hyperactivated fibroblast-like synoviocytes (FLS) that invade articular structures. Iguratimod (IGU), a conventional synthetic DMARD, is clinically effective, but its direct molecular target and impact on synovial cell-cell crosstalk remain unclear. We aimed to elucidate how IGU regulates FLS invasiveness and inflammatory signaling, identify its upstream target within the JAK-STAT pathway, and develop a prodrug with improved pharmacokinetics while preserving disease-modifying activity. - Source: PubMed
Publication date: 2026/08/03
Tao LinJiang WenHuang YulangFu XuefengWang HanYang HelinLi HaoTian ZixuanLiu DanWang ShaojieZhu Yue - The mechanisms sustaining chronic inflammation in rheumatoid arthritis (RA) remain incompletely understood. Here we show that branched-chain amino acid (BCAA) catabolism, mediated by the mitochondrial enzyme BCAT2, sustained interferon-driven macrophage activation in autoimmune arthritis. Multi-omics and histological analyses of individuals with active RA or sustained remission revealed that active disease was associated with systemic BCAA depletion, synovial branched-chain ketoacid accumulation and elevated BCAT2 expression in interferon-responsive synovial macrophages. Mechanistically, interferon-γ induced BCAT2 transcription through the transcription factor IRF1 in RA synovial macrophages. In human monocyte-derived macrophages, BCAT2-dependent BCAA catabolism elevated mitochondrial reactive oxygen species, which in turn restrained SHP-1 activity, prolonged STAT1 and STAT2 phosphorylation and drove inflammatory cytokine production. Furthermore, myeloid-specific deletion of Bcat2 ameliorated collagen antibody-induced arthritis in mice. Pharmacological targeting of this pathway with telmisartan suppressed persistent arthritis in methotrexate-treated mice. Together, our findings identified BCAT2-dependent amino acid catabolism as a potentially targetable metabolic pathway in autoimmune arthritis. - Source: PubMed
Publication date: 2026/07/31
Meng XiaohuiHan HaihuiYou WulinXin PengfeiJu YaCai LiangyuZhou LameiZhong ShengHu ZhuoyiChen ZhiyuQin WenleiGe YanhaoYao WeiXiao LianboZhang Yafeng - Japanese encephalitis virus (JEV) is a major cause of viral encephalitis and is associated with severe neuroinflammation and neurological damage. Despite extensive research on viral and host determinants of JEV pathogenesis, the influence of environmental factors on disease outcomes remains largely unexplored. This study investigated the impact of Cadmium (Cd), a ubiquitous and persistent environmental heavy metal exposure on JEV infection using in vitro and ex vivo approaches. The findings demonstrate that Cd pre-exposure markedly enhances viral infection, whereas co-exposure and post-exposure have minimal effects on viral infection. Mechanistically, Cd pre-exposure significantly suppressed key virus induced components of the innate antiviral response. Specifically, reduced activation of RIG-I led to the downregulation of TBK1 phosphorylation, which subsequently impaired IRF3 phosphorylation. This attenuation further resulted in decreased expression of STAT1 and STAT2, indicating disruption of downstream interferon signaling. Consistently, the expression of antiviral and inflammatory mediators, including TNF-α, IRF9, and ISG15, was markedly reduced. In contrast, ATF3, a known negative regulator of immune signaling, was significantly upregulated, suggesting its potential involvement in Cd-mediated suppression of antiviral immunity. Together, these results indicate that Cd does not directly enhance viral infection, but instead conditions host cells into an immunologically permissive state prior to infection. This toxicant-induced impairment of innate immunity creates a cellular environment that favours viral establishment and propagation. This study identifies environmental Cd exposure as an important modulator of antiviral immunity and provides insight into how toxicant-induced immune dysregulation can influence viral pathogenesis. - Source: PubMed
Publication date: 2026/07/31
Rawat YogitaGarg ManikaSood VikasKrishnan AnujaKamthan Mohan - Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes substantial morbidity in swine and may pose a zoonotic risk because of its cross-species transmission potential. Type I interferon (IFN-I) signaling is central to antiviral defense, initiated through the mitochondrial antiviral signaling (MAVS)-TBK1-IFN regulatory factor 3 (IRF3) axis and executed by the downstream JAK-STAT1-STAT2-IRF9 (ISGF3) pathway; however, how PDCoV circumvents both the induction and effector arms of this cascade remains incompletely understood. Here, we identify PDCoV nonstructural protein 13 (Nsp13) as a potent antagonist of IFN-I responses. Ectopic expression of Nsp13 markedly reduces IFN-β production and the expression of IFN-stimulated genes (ISGs, such as ISG56 and CXCL10). Mechanistically, Nsp13 directly binds the C-terminal domain (CTD) of TBK1 and competitively disrupts TBK1 interactions with IRF3 and MAVS. In addition, Nsp13 preferentially binds IRF9 and impairs its nuclear translocation, thereby inhibiting IFN-α-induced signaling. Notably, PDCoV Nsp13 exhibits a host-target binding profile similar to that of SARS-CoV-2 Nsp13, yet it does not alter TBK1 ubiquitination or protein stability. Collectively, these findings reveal a dual-layer immune evasion strategy whereby PDCoV Nsp13 suppresses both IFN induction and downstream signaling, and highlighting Nsp13 as a potential target for antiviral intervention. - Source: PubMed
Wang YingLan ShijinFang ZhenghuiYang ShixingWang XiaochunShen QuanLiu YuweiWu PingZhou ChenglinZhang WenJi Likai