TY - JOUR
T1 - Stat1 depends on transcriptional synergy with Sp1
AU - Look, Dwight C.
AU - Pelletier, Mark B.
AU - Tidwell, Rose M.
AU - Roswit, William T.
AU - Holtzman, Michael J.
PY - 1995/12/22
Y1 - 1995/12/22
N2 - 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-γ. 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.
AB - 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-γ. 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.
UR - http://www.scopus.com/inward/record.url?scp=0029557904&partnerID=8YFLogxK
U2 - 10.1074/jbc.270.51.30264
DO - 10.1074/jbc.270.51.30264
M3 - Article
C2 - 8530443
AN - SCOPUS:0029557904
SN - 0021-9258
VL - 270
SP - 30264
EP - 30267
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 51
ER -