Yc. Henderson et al., INTERFERON REGULATORY FACTOR-1 INDUCES THE EXPRESSION OF THE INTERFERON-STIMULATED GENES, British Journal of Haematology, 96(3), 1997, pp. 566-575
The interferon regulatory factor 1 (IRF-1) is a positive transcription
al 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 interf
eron-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 interfer
on-stimulated genes, 6-16 and 9-27, were increased in cells containing
increased levels of IRF-1. In addition, IRF-1 activates the expressio
n of IRF-2, a negative regulator of the type I interferon genes themse
lves. Two sequences were found in the IRF-2 promoter which were the bi
nding sites for IRF-1. Mutations in the oligonucleotide sequences of t
hese sites could abolish the binding of the IRF-1. These data suggeste
d that IRF-1 not only plays an important role in the induction of type
I interferon genes, but also in the activation of interferon-stimulat
ed genes.