Contribution of a TANK-Binding Kinase 1-Interferon (IFN) Regulatory Factor 7 Pathway to IFN-γ-Induced Gene Expression
Contribution of a TANK-Binding Kinase 1-Interferon (IFN) Regulatory Factor 7 Pathway to IFN-γ-Induced Gene Expression
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DOI：
10.1128/mcb.06021-11
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发表时间：
2012-03-01
影响因子：
5.3
通讯作者：
Decker, Thomas
中科院分区：
文献类型：
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作者：
Farlik, Matthias;Rapp, Birgit;Decker, Thomas
信号转导和转录激活因子（STAT）和干扰素调节因子（IRF）具有共同的靶基因。在这里，我们表明，Irf 7基因是由转录因子STAT 1和IRF 9在响应II型干扰素（IFN）IFN-γ。IRF 7与STAT 1和IRF 1协同作用，刺激IFN-γ诱导的STAT 1靶基因亚组的表达。IRF 7介导的Gbp 2基因的控制需要S/T激酶TANK结合激酶1（TBK 1）的存在和基础活性，而IRF 7与Gbp 2启动子的结合不需要。对Gbp 2启动子的RNA聚合酶II（Pol II）募集的分析揭示了IRF 7在IFN-γ应答的后期阶段的作用。为了支持IRF 7在建立有效抗菌应答中的作用，IFN-γ预处理的Irf 7（-/-）巨噬细胞在感染单核细胞增生李斯特菌后显示出增加的细菌负荷。因此，我们的数据描述了TBK 1的生物学相关基础活性，并将IRF 7鉴定为IFN-γ应答中的新参与者。
Signal transducers and activators of transcription (STATs) and interferon regulatory factors (IRFs) share common target genes. Here we show that the Irf7 gene is regulated by transcription factors STAT1 and IRF9 in response to the type II interferon (IFN) IFN-gamma. IRF7 cooperated with STAT1 and IRF1 to stimulate the expression of a subset of IFN-gamma-induced STAT1 target genes. IRF7-mediated control of the Gbp2 gene required the presence and basal activity of the S/T kinase TANK-binding kinase 1 (TBK1), whereas the binding of IRF7 to the Gbp2 promoter did not. Analysis of RNA polymerase II (Pol II) recruitment to the Gbp2 promoter revealed a role for IRF7 at later stages of the IFN-gamma response. In support of the role of IRF7 in establishing an effective antibacterial response, IFN-gamma-pretreated Irf7(-/-) macrophages showed an increased bacterial burden after infection with Listeria monocytogenes. Our data thus describe a biologically relevant basal activity of TBK1 and identify IRF7 as a novel player in the IFN-gamma response.