Cooperative interaction of NF-kappaB and C/EBP binding sites is necessary for manganese superoxide dismutase gene transcription mediated by lipopolysaccharide and interferon-gamma.
Expression of the manganese superoxide dismutase (Mn-SOD) is induced by pro-inflammatory cytokines. We investigated the cis-acting elements within a tumor necrosis factor-responsive element (TNFRE) which was identified in the second intron of the murine Mn-SOD gene. Site-directed mutagenesis, reporter plasmid transfection studies and electrophoretic mobility shift assays demonstrated that inducible transcription factors enhanced the transcriptional activity of the Mn-SOD gene through the TNFRE. The cooperation between proteins binding to the newly identified NF-kappaB and C/EBP sites led to synergistic gene transcription. This report provides the first evidence that cooperation between two distinct cis-acting elements may be required for induction of Mn-SOD gene expression mediated by lipopolysaccharide and interferon-gamma.
Maehara
K
K
Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Aichi, Japan.
Hasegawa
T
T
Xiao
H
H
Takeuchi
A
A
Abe
R
R
Isobe
K
K
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015971:Gene Expression Regulation, Enzymologic; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008345:Manganese; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000235:genetics*; D051996:Transcription Factor RelA; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D051996:Transcription Factor RelA; D008345:Manganese; D007371:Interferon-gamma; D013482:Superoxide Dismutase