Grass Carp (Ctenopharyngodon idella) KAT8 Inhibits IFN 1 Response Through Acetylating IRF3/IRF7.
Grass Carp (Ctenopharyngodon idella) KAT8 Inhibits IFN 1 Response Through Acetylating IRF3/IRF7.
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草鲤（ctenopharyngodon idella）KAT8通过乙酰化IRF3/IRF7抑制IFN 1响应。
DOI：
10.3389/fimmu.2021.808159
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发表时间：
2021
影响因子：
7.3
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Li M;Hu J;Mao H;Li D;Jiang Z;Sun Z;Yu T;Hu C;Xu X
翻译后修饰（PTM），如磷酸化和泛素化等，已报道调节IRF 3和IRF 7的活性。在本研究中，我们在草鱼中发现了一种乙酰转移酶KAT 8（CiKAT 8，MW 286472），它可以乙酰化IRF 3/IRF 7，从而抑制IFN 1的反应。在poly I：C、B-DNA或Z-DNA刺激以及GCRV（菌株873）或SVCV感染下，CiKAT 8表达在细胞中上调。KAT 8的乙酰转移酶结构域（MYST结构域）通过与IRF 3和IRF 7直接相互作用促进IRF 3和IRF 7的乙酰化。因此，该结构域对KAT 8功能至关重要。预期不含MYST结构域的KAT 8（KAT 8-△264-487）在细胞核中呈颗粒状聚集，不能下调IFN 1的表达。亚细胞定位分析显示KAT 8蛋白均匀分布于细胞核内。此外，我们发现KAT 8抑制IRF 3和IRF 7向ISRE反应元件的募集。综上所述，我们的研究结果表明，草鱼KAT 8通过乙酰化IRF 3和IRF 7，使ISRE反应元件与IRF 3和IRF 7发生低亲和力的相互作用，从而抑制核酸诱导的天然免疫应答。
Post-translational modifications (PTMs), such as phosphorylation and ubiquitination, etc., have been reported to modulate the activities of IRF3 and IRF7. In this study, we found an acetyltransferase KAT8 in grass carp (CiKAT8, MW286472) that acetylated IRF3/IRF7 and then resulted in inhibition of IFN 1 response. CiKAT8 expression was up-regulated in the cells under poly I:C, B-DNA or Z-DNA stimulation as well as GCRV(strain 873) or SVCV infection. The acetyltransferase domain (MYST domain) of KAT8 promoted the acetylation of IRF3 and IRF7 through the direct interaction with them. So, the domain is essential for KAT8 function. Expectedly, KAT8 without MYST domain (KAT8-△264-487) was granularly aggregated in the nucleus and failed to down-regulate IFN 1 expression. Subcellular localization analysis showed that KAT8 protein was evenly distributed in the nucleus. In addition, we found that KAT8 inhibited the recruitment of IRF3 and IRF7 to ISRE response element. Taken together, our findings revealed that grass carp KAT8 blocked the activities of IRF3 and IRF7 by acetylating them, resulting in a low affinity interaction of ISRE response element with IRF3 and IRF7, and then inhibiting nucleic acids-induced innate immune response.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
16.6
作者：
Ageta-Ishihara, Natsumi;Miyata, Takaki;Ohshima, Chika;Watanabe, Masahiko;Sato, Yoshikatsu;Hamamura, Yuki;Higashiyama, Tetsuya;Mazitschek, Ralph;Bito, Haruhiko;Kinoshita, Makoto
通讯作者：
Kinoshita, Makoto
对 RNA 病毒的先天免疫受 RIG-I 和 MDA5 的暂时且可逆的 sumoylation 调节
DOI：
10.1084/jem.20161015
发表时间：
2017-04-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hu MM;Liao CY;Yang Q;Xie XQ;Shu HB
通讯作者：
Shu HB
影响因子：
6.7
作者：
Chang TH;Kubota T;Matsuoka M;Jones S;Bradfute SB;Bray M;Ozato K
通讯作者：
Ozato K
影响因子：
64.8
作者：
Honda, K;Ohba, Y;Taniguchi, T
通讯作者：
Taniguchi, T