自2008年STING的发现以来，大量研究已经仔细分析了STING的结构，形成了一个优雅的STING激活模型，在这个模型中，cGAMP结合后，STING向内旋转至配体结合口袋，关闭其配体结合口袋，并释放其C-末端以招募TBK1和IRF3。2013年，发现了cGAS在哺乳动物细胞中的存在，并揭示其合成cGAMP作为第二信使直接激活STING的能力。此后，cGA...
STING的激活,会招募TANK结合激酶1 (TBK1),它能磷酸化干扰素调节因子3 (IRF3)和核因子-kappa B (NF-κB)等转录因子,诱导I型干扰素(IFN)和促炎细胞因子包括肿瘤坏死因子-α (TNF-α)、白细胞介素1β (IL-1β)和IL-6的产生。越...
磷酸化的IRF3形成二聚体,转移至细胞核,诱导下游I型干扰素(type I interferon,IFN-Ⅰ)和干扰素刺激基因(interferon stimulatory genes,ISGs)的转录表达,启动先天性免疫反应[13]。此外,STING还可激活经典的NF-κB(nuclear factor kappa-B,...
活化的 STING 可迁移并激活 TBK1,诱导 IRF3 和 NF-κB 的磷酸化,从而触发促炎细胞因子的转录。与此相一致,scRNA-seq 数据也显示转录因子 Nfkb1 和 Irf3 的调节子活性在 Gsdmd-/-ApoE-/- 小鼠中降低,这些降低主要发生在 M1 巨噬细胞中。因此,作者推测 GSDMD 在氧化-LDL 诱导的 MPMs 中通过线粒体穿孔调节...
Furthermore, the same phenomenon was also observed in Irf3−/− macrophages (Supplementary Fig. 1B) and cgas−/− L929 cells (Supplementary Fig. 1C), which means the cGAS-STING pathway and type I IFNs were not indispensable for the regulation of UFL1 expression. Previous reports ...
Most prominently, the outcome of cGAS signalling is the activation of inflammatory transcription through interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB). In addition, the cGAS-STING pathway can lead to the direct modulation of cellular processes independently of ...
IRF3-JUN转录因子复合物有利于ACOD1上调 作者接下来试图确定负责 STING1 依赖性 ACOD1 上调的转录因子。作者专注于干扰素调节因子 3 (IRF3) 和核因子-kappa B (NF-κB),这两种调节 STING1 依赖性细胞因子表达的众所周知的转录因子 (DNA sensing by the cGAS-STING pathway in health and disease. Nat. Rev...
Abbreviations: cGAMP, 2′,3′-cyclic GMP-AMP; ER, endoplasmic reticulum; IRF3, interferon regulatory factor 3; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TBK1, TANK-binding kinase 1 Full size image Biology and expression of protein STING and its pathway The ...
TBK1 also phosphorylates Iκβα, an inhibitor of the transcription factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), marking it for proteasomal degradation; Iκβα degradation releases NF-κB, which translocates together with IRF3 into the nucleus, providing a ...
4J). GSEA analysis revealed that ZMD was associated with the NF-kappa B signaling pathway, the regulation of B cell activation, the regulation of cell killing, the regulation of immune response to tumor cell, the regulation of T cell mediated cytotoxicity and T cell activation (Figure S6). ...