Interferon regulatory factor 1 induces the expression of the interferon-stimulated genes.
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.
Henderson
Y C
YC
Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston, U.S.A.
Chou
M
M
Deisseroth
A B
AB
D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007372:Interferons / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D007372:Interferons