Activation of transcription factors by interferon-alpha in a cell-free system.
The signal transduction mechanisms of interferons (IFNs) remain unclear partly because no effect of IFN has been reproducible in a cell-free system. IFN-alpha rapidly induces the transcription of a set of early response genes, and a multicomponent transcriptional activator, interferon stimulated gene factor 3 (ISGF3), is activated within minutes after binding of IFN-alpha to its receptor. A system was developed in which IFN-alpha activated ISGF3 in homogenates of HeLa cells. Subcellular fractionation revealed that incubation of a plasma membrane-enriched fraction with IFN-alpha was sufficient to activate the regulatory subcomponent of ISGF3.
David
M
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Division of Cytokine Biology, Center for Biologics Evaluation and Research, Bethesda, MD 20892.
Larner
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D001483:Base Sequence; D002474:Cell-Free System; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015345:Oligonucleotide Probes; D014157:Transcription Factors / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D015345:Oligonucleotide Probes; D014157:Transcription Factors; D007371:Interferon-gamma