Activation of the rat serine proteinase inhibitor 3 gene by interferon gamma via the interleukin 6-responsive element.
Transcription of rat serine proteinase inhibitor 3 (SPI-3) gene is rapidly induced in the liver in response to inflammation. Treatment of rat hepatoma H-35 cells with interferon gamma (INF gamma) results in the immediate induction of this gene, with its 147 bp-long promoter being sufficient for activation. Within this promoter we have identified an IFN gamma-responsive element which maps to the signal transducer and activator of transcription (Stat)3-binding site. Mutation of this element causes a loss of responsiveness to IFN gamma, whereas fusion to a heterologous promoter confers a positive response on IFN gamma. The latter apparently induces the binding of a protein, identified as Stat1, to the described element, which gradually decreases within 24 h. Thus the induction of the SPI-3 gene by IFN gamma correlates with the binding of Stat1 to a specific element which, in turn, binds Stat3 in response to interleukin 6.
Kordula
T
T
Institute of Molecular Biology, Jagiellonian University, Krakow, Poland.
Travis
J
J
D000818:Animals; D001483:Base Sequence; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011485:Protein Binding; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D015842:Serine Proteinase Inhibitors; D007371:Interferon-gamma