Single amino acid change in STING leads to constitutive active signaling.
Single amino acid change in STING leads to constitutive active signaling.
复制标题
DOI：
10.1371/journal.pone.0120090
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang CY
中科院分区：
文献类型：
--
作者：
Tang ED;Wang CY
免疫系统响应胞浆DNA产生细胞因子在宿主防御、自身免疫性疾病和癌症免疫原性中发挥着重要作用。最近，已经鉴定了依赖于内质网接头和环状二核苷酸传感器蛋白STING的细胞溶质DNA信号传导途径。胞质DNA与环-GMP-AMP合酶（cGAS）的缔合激活其酶活性以从GTP和ATP合成环二核苷酸第二信使cGAMP。通过STING直接检测cGAMP触发IRF 3和NF-kB的激活，以及I型干扰素和促炎细胞因子的产生。STING如何能够介导下游信号传导的机制仍然不完全清楚，尽管已经表明二聚化是先决条件。在这里，我们确定了一个单一的氨基酸变化，在STING赋予组成型活性信号。该突变似乎增强了STING二聚化和与其下游靶TBK 1缔合的能力。
The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS) activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.
登录
查看更多内容
影响因子：
8.8
作者：
Zhang X;Wu J;Du F;Xu H;Sun L;Chen Z;Brautigam CA;Zhang X;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1056/nejmoa1312625
发表时间：
2014-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Liu Y;Jesus AA;Marrero B;Yang D;Ramsey SE;Sanchez GAM;Tenbrock K;Wittkowski H;Jones OY;Kuehn HS;Lee CR;DiMattia MA;Cowen EW;Gonzalez B;Palmer I;DiGiovanna JJ;Biancotto A;Kim H;Tsai WL;Trier AM;Huang Y;Stone DL;Hill S;Kim HJ;St Hilaire C;Gurprasad S;Plass N;Chapelle D;Horkayne-Szakaly I;Foell D;Barysenka A;Candotti F;Holland SM;Hughes JD;Mehmet H;Issekutz AC;Raffeld M;McElwee J;Fontana JR;Minniti CP;Moir S;Kastner DL;Gadina M;Steven AC;Wingfield PT;Brooks SR;Rosenzweig SD;Fleisher TA;Deng Z;Boehm M;Paller AS;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
DOI：
10.1126/science.1244040
发表时间：
2013-09-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li XD;Wu J;Gao D;Wang H;Sun L;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
32.4
作者：
Gall A;Treuting P;Elkon KB;Loo YM;Gale M Jr;Barber GN;Stetson DB
通讯作者：
Stetson DB