Multiple functions of the IKK-related kinase IKKε in interferon-mediated antiviral immunity
Multiple functions of the IKK-related kinase IKKε in interferon-mediated antiviral immunity
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DOI：
10.1126/science.1136567
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发表时间：
2007-03-02
期刊：
影响因子：
56.9
通讯作者：
Maniatis, Tom
中科院分区：
文献类型：
--
作者：
tenOever, Benjamin R.;ng, Sze-Li Ng;Maniatis, Tom
IKK epsilon是一种IKK（核因子κ B激酶抑制剂）相关激酶，与病毒诱导干扰素β (IFN β)有关。我们报道，尽管缺乏IKK epsilon的小鼠产生正常数量的IFN β，但由于IFN信号通路的缺陷，它们对病毒感染易感。具体来说，在缺乏IKK epsilon的情况下，I型ifn刺激基因的一个子集不会被激活，因为干扰素刺激基因因子3复合体（ISGF3）不与受影响基因的启动子元件结合。我们证明IKK epsilon可被IFN β激活，并且IKK epsilon可直接磷酸化ISGF3的一个组成部分——信号换能器和转录激活器1 （STAT1）。我们得出结论，ikkepsilon在ifn诱导的抗病毒转录反应中起关键作用。
IKK epsilon is an IKK ( inhibitor of nuclear factor kappa B kinase)-related kinase implicated in virus induction of interferon-beta (IFN beta). We report that, although mice lacking IKK epsilon produce normal amounts of IFN beta, they are hypersusceptible to viral infection because of a defect in the IFN signaling pathway. Specifically, a subset of type I IFN-stimulated genes are not activated in the absence of IKK epsilon because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKK epsilon is activated by IFN beta and that IKK epsilon directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKK epsilon plays a critical role in the IFN-inducible antiviral transcriptional response.