Henderson Y C, Chou M, Deisseroth A B
Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston, U.S.A.
Br J Haematol. 1997 Mar;96(3):566-75. doi: 10.1046/j.1365-2141.1997.d01-2057.x.
The interferon regulatory factor 1 (IRF-1) is a positive transcriptional regulatory protein which acts in the interferon signal transduction pathway to activate the transcription of the type I interferon genes by binding to the PRDI response element. The aim of this study was to explore the role of IRF-1 in regulating the expression of other interferon-stimulated genes in the interferon signal transduction pathway. A transient transfection assay was used to show that IRF-1 induced the expression of interferon-stimulated genes. The induction was a direct result of IRF-1 binding to the promoters of the interferon-stimulated response element (ISRE). The levels of endogenous mRNA of two interferon-stimulated genes, 6-16 and 9-27, were increased in cells containing increased levels of IRF-1. In addition, IRF-1 activates the expression of IRF-2, a negative regulator of the type I interferon genes themselves. Two sequences were found in the IRF-2 promoter which were the binding sites for IRF-1. Mutations in the oligonucleotide sequences of these sites could abolish the binding of the IRF-1. These data suggested that IRF-1 not only plays an important role in the induction of type I interferon genes, but also in the activation of interferon-stimulated genes.
干扰素调节因子1（IRF-1）是一种正向转录调节蛋白，它在干扰素信号转导途径中发挥作用，通过与PRDI反应元件结合来激活I型干扰素基因的转录。本研究的目的是探讨IRF-1在调节干扰素信号转导途径中其他干扰素刺激基因表达方面的作用。采用瞬时转染试验表明IRF-1可诱导干扰素刺激基因的表达。这种诱导是IRF-1与干扰素刺激反应元件（ISRE）启动子结合的直接结果。在IRF-1水平升高的细胞中，两种干扰素刺激基因6-16和9-27的内源性mRNA水平升高。此外，IRF-1可激活I型干扰素基因自身的负调节因子IRF-2的表达。在IRF-2启动子中发现了两个序列，它们是IRF-1的结合位点。这些位点的寡核苷酸序列发生突变可消除IRF-1的结合。这些数据表明，IRF-1不仅在I型干扰素基因的诱导中起重要作用，而且在干扰素刺激基因的激活中也起重要作用。
