Transcriptional regulation of the MAIL gene in LPS-stimulated RAW264 mouse macrophages
Transcriptional regulation of the MAIL gene in LPS-stimulated RAW264 mouse macrophages
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DOI：
10.1016/j.gene.2004.07.032
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发表时间：
2004-11-10
期刊：
影响因子：
3.5
通讯作者：
Syuto, B
中科院分区：
文献类型：
--
作者：
Ito, T;Morimatsu, M;Syuto, B
Ikappa B抑制核因子κ B（NF-κ B），已知NF-κ B调节各种基因的表达，包括参与炎症的基因。最近，一个新的IkappaB家族蛋白，“分子具有锚蛋白重复诱导脂多糖”（MAIL），被确定。MAIL是一种核作用的诱导蛋白，与典型的IkappaB蛋白不同。然而，脂多糖（LPS）诱导的机制尚不清楚。利用位于MAIL基因上游的LPS反应区，我们研究了MAIL诱导的机制。MAIL的表达受NF-κ B的强烈调节，部分受CREB的调节。此外，缺失、点突变和结合分析表明，位于-229至-220 bp的NF-κ B结合位点是MAIL表达的一个重要靶点。MAIL蛋白的过表达抑制了LPS诱导的MAIL基因启动子活性。这些数据表明，MAIL的表达强烈上调NF-κ B，它是控制，至少部分地，通过自动调节机制。(C)2004 Elsevier B. V.保留所有权利。
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 a n 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. (C) 2004 Elsevier B.V. All rights reserved.