A novel transcript isoform of STING that sequesters cGAMP and dominantly inhibits innate nucleic acid sensing.
A novel transcript isoform of STING that sequesters cGAMP and dominantly inhibits innate nucleic acid sensing.
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DOI：
10.1093/nar/gky186
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发表时间：
2018-05-04
影响因子：
14.9
通讯作者：
Jin DY
中科院分区：
文献类型：
--
作者：
Wang PH;Fung SY;Gao WW;Deng JJ;Cheng Y;Chaudhary V;Yuen KS;Ho TH;Chan CP;Zhang Y;Kok KH;Yang W;Chan CP;Jin DY
STING是哺乳动物细胞中先天核酸传感的核心适配器，不同的传感途径汇聚在其上以诱导I型干扰素（IFN）的产生。特别地，STING被2′3′-cGAMP激活，2 ′ 3′-cGAMP是一种含有混合磷酸二酯键并由细胞质DNA传感器cGAS产生的环状二核苷酸。在这里，我们报道了一种新的转录异构体的STING命名STING-β，主要抑制先天核酸传感。无跨膜结构域的STING-β在各种人体组织中以低水平广泛表达，并且STING-β的病毒诱导与IFN-β产生呈负相关。STING-β的表达在狼疮患者中下降，其中I型IFN通常过度产生。STING-β抑制各种免疫刺激剂（包括环状二核苷酸、DNA、RNA和病毒）对IFN、IFN刺激的基因和其他细胞因子的诱导，而STING-β的消耗显示出相反的效果。STING-β与STING-α相互作用，拮抗STING-α的抗病毒作用。STING-β还与TBK 1相互作用，并阻止其与STING-α、TRIF或其他转导物结合。此外，STING-β与2′3′-cGAMP结合并阻碍其与STING-α的结合和活化，从而抑制IFN-β的产生。总之，STING-β螯合2′3′-cGAMP第二信使和其他转导分子以主要抑制先天核酸传感。
STING is a core adaptor in innate nucleic acid sensing in mammalian cells, on which different sensing pathways converge to induce type I interferon (IFN) production. Particularly, STING is activated by 2′3′-cGAMP, a cyclic dinucleotide containing mixed phosphodiester linkages and produced by cytoplasmic DNA sensor cGAS. Here, we reported on a novel transcript isoform of STING designated STING-β that dominantly inhibits innate nucleic acid sensing. STING-β without transmembrane domains was widely expressed at low levels in various human tissues and viral induction of STING-β correlated inversely with IFN-β production. The expression of STING-β declined in patients with lupus, in which type I IFNs are commonly overproduced. STING-β suppressed the induction of IFNs, IFN-stimulated genes and other cytokines by various immunostimulatory agents including cyclic dinucleotides, DNA, RNA and viruses, whereas depletion of STING-β showed the opposite effect. STING-β interacted with STING-α and antagonized its antiviral function. STING-β also interacted with TBK1 and prevented it from binding with STING-α, TRIF or other transducers. In addition, STING-β bound to 2′3′-cGAMP and impeded its binding with and activation of STING-α, leading to suppression of IFN-β production. Taken together, STING-β sequesters 2′3′-cGAMP second messenger and other transducer molecules to inhibit innate nucleic acid sensing dominantly.
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DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Chen, Honghe;Pei, Rongjuan;Chen, Xinwen
通讯作者：
Chen, Xinwen
影响因子：
15.9
作者：
Jeremiah, Nadia;Neven, Benedicte;Rieux-Laucat, Frederic
通讯作者：
Rieux-Laucat, Frederic
DOI：
10.1073/pnas.1323414111
发表时间：
2014-02-04
影响因子：
11.1
作者：
Kalamvoki, Maria;Roizman, Bernard
通讯作者：
Roizman, Bernard
影响因子：
29.7
作者：
Crowl JT;Gray EE;Pestal K;Volkman HE;Stetson DB
通讯作者：
Stetson DB