Critical role of a common transcription factor, IRF-1, in the regulation of IFN-beta and IFN-inducible genes.
Interferon regulatory factor 1 (IRF-1) is a protein that binds to cis-elements within the promoter of interferon (IFN)-beta and some IFN-inducible genes. We used a human fibroblast line, GM-637, to generate stable transfectants constitutively expressing IRF-1 mRNA in either the sense or antisense orientation. Upon induction with poly-(I).poly(C) or Newcastle disease virus, cells expressing sense IRF-1 mRNA produced significantly higher levels of IFN-beta mRNA and protein than control cells, whereas cells expressing antisense IRF-1 mRNA produced little or no IFN-beta mRNA and protein. Furthermore, clear differences were seen among the transfectants in the level of expression of two IFN-induced genes (2'-5'-oligoadenylate synthetase and class I HLA). Our data show that IRF-1 is essential for the induced expression of the IFN-beta gene. The results also indicate an important role of IRF-1 in the expression of IFN-inducible genes and suggest a role for IRF-1 in many other cytokine actions.
Department of Microbiology, New York University Medical Center, NY 10016.
L F
LF
Reis
H
H
Harada
J D
JD
Wolchok
T
T
Taniguchi
J
J
Vilcek
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000494:pharmacology*; D008285:Major Histocompatibility Complex / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D012313:RNA; D016372:RNA, Antisense; D012867:Skin / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D016372:RNA, Antisense; C039919:RNA, recombinant; D014157:Transcription Factors; D012313:RNA; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase