The competitive binding of STAT3 and NF-kappaB on an overlapping DNA binding site.
Interleukin-1 (IL-1) and interleukin-6 (IL-6), two early-response cytokines expressed during an acute inflammatory reaction, regulate the expression of several acute phase proteins (APP) in the liver. IL-1 relays its signal to specific genes via NF-kappaB, whereas IL-6 sends its signal to the nucleus via STAT1alpha and STAT3. Interestingly, overlapping binding sites for STAT3 and NF-kappaB can be found on promoters of several APP genes. We show here that both STAT3 and NF-kappaB are active during inflammation and are capable of binding to a STAT3/NF-kappaB overlapping DNA motif derived from the alpha2-macroglobulin gene promoter. In vitro binding assays demonstrated that NF-kappaB competes with STAT3 binding on this probe. Our results suggest that these transcription factors regulate each others' function through competition for overlapping DNA binding sites.
Zhang
Z
Z
Department of Cell Biology, University of Alabama at Birmingham, 35294, USA.
Fuller
G M
GM
D000209:Acute-Phase Proteins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D007249:Inflammation; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D004247:DNA