STAT1 DEPENDS ON TRANSCRIPTIONAL SYNERGY WITH SP1

STAT (Signal transducer and activator of transcription) proteins combi ne with cytokine receptors and receptor-associated kinases in distinct protein/protein interactions that are critical for STAT-dependent sig nal transduction events, but the nature of any subsequent STAT interac tions 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 site s for Stat1 (the first member of the STAT family) and the transcriptio nal activator Sp1 are both required for full activation of the interce llular adhesion molecule-1 gene by interferon-gamma, Thus, Stat1 bindi ng to DNA cannot by itself be equated with biologic actions of Stat1. In co-immunoprecipitation experiments, are also obtained evidence of d irect and selective Stat1/Sp1 interaction (in primary culture cells wi thout overexpression), further indicating that Stat1/Sp1 synergy confe rs an element of specificity in the pathway leading to cytokine-activa ted transcription and cytokine-dependent immunity and inflammation.