期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：52
页码：21170-21175
DOI：10.1073/pnas.1119137109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Virus infection induces the production of type I and type II interferons (IFN-I and IFN-II), cytokines that mediate the antiviral response. IFN-I (IFN- and IFN-{beta}) induces the assembly of IFN-stimulated gene factor 3 (ISGF3), a multimeric transcriptional activation complex composed of STAT1, STAT2, and IFN regulatory factor 9. IFN-II (IFN-{gamma}) induces the homodimerization of STAT1 to form the gamma-activated factor (GAF) complex. ISGF3 and GAF bind specifically to unique regulatory DNA sequences located upstream of IFN-I- and IFN-II-inducible genes, respectively, and activate the expression of distinct sets of antiviral genes. The balance between type I and type II IFN pathways plays a critical role in orchestrating the innate and adaptive immune systems. Here, we show that the phosphorylation of STAT1 by I{kappa}B kinase epsilon (IKK{varepsilon}) inhibits STAT1 homodimerization, and thus assembly of GAF, but does not disrupt ISGF3 formation. Therefore, virus and/or IFN-I activation of IKK{varepsilon} suppresses GAF-dependent transcription and promotes ISGF3-dependent transcription. In the absence of IKK{varepsilon
关键词：JAK/STAT ; STAT dimerization ; IFN-stimulated response element ; gamma-activated sequences
