Abstract
STAT (signal transducer and activator of transcription) proteins combine with cytokine receptors and receptor-associated kinases in distinct protein/protein interactions that are critical for STAT-dependent signal transduction events, but the nature of any subsequent STAT interactions with DNA-binding proteins in the nucleus is less certain. Based on assays of DNA/protein binding and activity of transfected reporter plasmids, we determined that occupation of contiguous DNA-binding sites for Stat1 (the first member of the STAT family) and the transcriptional activator Sp1 are both required for full activation of the intercellular adhesion molecule-1 gene by interferon-gamma. Thus, Stat1 binding to DNA cannot by itself be equated with biologic actions of Stat1. In co-immunoprecipitation experiments, we also obtained evidence of direct and selective Stat1/Sp1 interaction (in primary culture cells without overexpression), further indicating that Stat1/Sp1 synergy confers an element of specificity in the pathway leading to cytokine-activated transcription and cytokine-dependent immunity and inflammation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Binding Sites
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Cell Line
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Chloramphenicol O-Acetyltransferase / analysis
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Chloramphenicol O-Acetyltransferase / biosynthesis
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / metabolism*
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Gene Expression / drug effects
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Humans
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Intercellular Adhesion Molecule-1 / biosynthesis*
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Intercellular Adhesion Molecule-1 / genetics
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Interferon-gamma / pharmacology
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Luciferases / analysis
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Luciferases / biosynthesis
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Molecular Sequence Data
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Oligodeoxyribonucleotides
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Polymerase Chain Reaction
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins
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Repetitive Sequences, Nucleic Acid
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STAT1 Transcription Factor
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Signal Transduction
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Trans-Activators / biosynthesis
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Trans-Activators / metabolism*
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Transcription, Genetic*
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Transfection
Substances
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DNA-Binding Proteins
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Oligodeoxyribonucleotides
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Recombinant Fusion Proteins
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Recombinant Proteins
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STAT1 Transcription Factor
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STAT1 protein, human
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Trans-Activators
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Intercellular Adhesion Molecule-1
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Interferon-gamma
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Luciferases
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Chloramphenicol O-Acetyltransferase