Abstract
IkappaB inhibits nuclear factor kappa B (NF-kappaB), which is known to regulate the expression of various genes, including genes involved in inflammation. Recently, a novel IkappaB family protein, 'molecule possessing ankyrin repeats induced by lipopolysaccharide' (MAIL), was identified. MAIL is a nuclear-acting, inducible protein, unlike typical IkappaB proteins. However, the mechanism of its induction by lipopolysaccharide (LPS) is unclear. Using the LPS-reactive region located upstream from the MAIL gene, we investigated the mechanism of MAIL induction. MAIL expression was strongly regulated by NF-kappaB and partly regulated by CREB. Furthermore, deletion, point mutation and binding analyses revealed that the NF-kappaB binding site located at -229 to -220 bp is an essential target of MAIL expression. Overexpression of MAIL protein suppressed the LPS-induced promoter activity of the MAIL gene. These data indicate that MAIL expression is strongly upregulated by NF-kappaB, and it is controlled, at least in part, by an autoregulation mechanism.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Base Sequence
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Binding Sites / genetics
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Cell Line
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Cyclic AMP Response Element-Binding Protein
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Electrophoretic Mobility Shift Assay
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Gene Expression Regulation / drug effects
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Lipopolysaccharides / pharmacology*
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Luciferases / genetics
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Luciferases / metabolism
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Macrophages / cytology
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Macrophages / drug effects*
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Macrophages / metabolism
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Mice
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Mice, Inbred Strains
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NF-kappa B / metabolism
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Point Mutation
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Promoter Regions, Genetic / genetics
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Deletion
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Transcription Factors / metabolism
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Transcription, Genetic / genetics*
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Creb1 protein, mouse
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Cyclic AMP Response Element-Binding Protein
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Lipopolysaccharides
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NF-kappa B
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Nfkbiz protein, mouse
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Nuclear Proteins
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Protein Isoforms
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Recombinant Fusion Proteins
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Transcription Factors
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Luciferases