Interferon regulatory factor 1 induces the expression of the interferon-stimulated genes.

ABSTRACT

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.