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Publication : Contribution of a TANK-binding kinase 1-interferon (IFN) regulatory factor 7 pathway to IFN-γ-induced gene expression.

First Author  Farlik M Year  2012
Journal  Mol Cell Biol Volume  32
Issue  6 Pages  1032-43
PubMed ID  22252317 Mgi Jnum  J:183707
Mgi Id  MGI:5319124 Doi  10.1128/MCB.06021-11
Citation  Farlik M, et al. (2012) Contribution of a TANK-binding kinase 1-interferon (IFN) regulatory factor 7 pathway to IFN-gamma-induced gene expression. Mol Cell Biol 32(6):1032-43
abstractText  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.
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