Interaction of stat6 and NF-kappaB: direct association and synergistic activation of interleukin-4-induced transcription
Department of Molecular Genetics and Microbiology
Binding Sites; Cell Line; DNA; Drug Synergism; Glutathione Transferase; Humans; Interleukin-4; NF-kappa B; NF-kappa B p50 Subunit; Protein Binding; Recombinant Fusion Proteins; STAT6 Transcription Factor; Signal Transduction; Trans-Activators; Transcription Factor RelA; *Transcription, Genetic; Tumor Cells, Cultured
Life Sciences | Medicine and Health Sciences | Women's Studies
Signal transducer and activator of transcription 6 (Stat6) and NF-kappaB are widely distributed transcription factors which are induced by different stimuli and bind to distinct DNA sequence motifs. Interleukin-4 (IL-4), which activates Stat6, synergizes with activators of NF-kappaB to induce IL-4-responsive genes, but the molecular mechanism of this synergy is poorly understood. Using glutathione S-transferase pulldown assays and coimmunoprecipitation techniques, we find that NF-kappaB and tyrosine-phosphorylated Stat6 can directly bind each other in vitro and in vivo. An IL-4-inducible reporter gene containing both cognate binding sites in the promoter is synergistically activated in the presence of IL-4 when Stat6 and NF-kappaB proteins are coexpressed in human embryonic kidney 293 (HEK 293) cells. The same IL-4-inducible reporter gene is also synergistically activated by the endogenous Stat6 and NF-kappaB proteins in IL-4-stimulated I.29mu B lymphoma cells. Furthermore, Stat6 and NF-kappaB bind cooperatively to a DNA probe containing both sites, and the presence of a complex formed by their cooperative binding correlates with the synergistic activation of the promoter by Stat6 and NF-kappaB. We conclude that the direct interaction between Stat6 and NF-kappaB may provide a basis for synergistic activation of transcription by IL-4 and activators of NF-kappaB.
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Citation: Mol Cell Biol. 1998 Jun;18(6):3395-404.
Shen, Ching-Hung and Stavnezer, Janet, "Interaction of stat6 and NF-kappaB: direct association and synergistic activation of interleukin-4-induced transcription" (1998). Women’s Health Research Faculty Publications. Paper 201.