Reference - Detail
|Author||Ito T, Morimatsu M, Oonuma T, Shiina T, Kitamura H, Syuto B.|
|Title||Transcriptional regulation of the MAIL gene in LPS-stimulated RAW264 mouse macrophages.|
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.
|MeSH||Adaptor Proteins, Signal Transducing Animals Base Sequence Binding Sites / genetics Cell Line Cyclic AMP Response Element-Binding Protein Electrophoretic Mobility Shift Assay Gene Expression Regulation / drug effects Lipopolysaccharides / pharmacology* Luciferases / genetics Luciferases / metabolism Macrophages / cytology Macrophages / drug effects* Macrophages / metabolism Mice Mice, Inbred Strains NF-kappa B / metabolism Nuclear Proteins / genetics* Nuclear Proteins / metabolism Point Mutation Promoter Regions, Genetic / genetics Protein Isoforms / genetics Protein Isoforms / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Sequence Deletion Transcription Factors / metabolism Transcription, Genetic / genetics* Transfection|
|WOS Category||GENETICS & HEREDITY|
|Human and Animal Cells||RAW 264|