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首页> 外文期刊>Molecular and Cellular Biology >Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines.
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Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines.

机译：不依赖环AMP的ATF家族成员与NF-κB相互作用，并在响应细胞因子的E-选择素启动子的激活中起作用。

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We previously reported that NF-kappa B and a complex we referred to as NF-ELAM1 play a central role in cytokine-induced expression of the E-selectin gene. In this study we identify cyclic AMP (cAMP)-independent members of the ATF family binding specifically to the NF-ELAM1 promoter element. The NF-ELAM1 element (TGACATCA) differs by a single nucleotide substitution from the cAMP-responsive element consensus sequence. We demonstrate that this sequence operates in a cAMP-independent manner to induce transcription and thus define it as a non-cAMP-responsive element (NCRE). We show that ATFa is a component of the NF-ELAM1 complex and its overexpression activates the E-selectin promoter. In addition, ATFa, ATF2, and ATF3 interact directly with NF-kappa B in vitro, linking two unrelated families of transcription factors in a novel protein-protein interaction. Furthermore, we demonstrate that the ability of overexpressed NF-kappa B to transactivate the E-selectin promoter in vivo is dependent on the NF-ELAM1 complex. Our results suggest that a direct interaction between ATFs and NF-kappa B is, at least in part, the mechanism by which these factors specifically regulate E-selectin promoter activity.
机译：我们先前曾报道过NF-κB和我们称为NF-ELAM1的复合体在细胞因子诱导的E-选择素基因表达中起着核心作用。在这项研究中，我们确定ATF家族的环状AMP（cAMP）独立成员与NF-ELAM1启动子元件特异性结合。 NF-ELAM1元件（TGACATCA）与cAMP响应元件共有序列的区别是单核苷酸取代。我们证明该序列以cAMP独立的方式操作以诱导转录，从而将其定义为非cAMP反应元件（NCRE）。我们表明，ATFa是NF-ELAM1复杂的一个组成部分，其过表达激活E-选择蛋白启动子。此外，ATFa，ATF2和ATF3在体外直接与NF-κB相互作用，从而以新颖的蛋白质-蛋白质相互作用将两个无关的转录因子家族连接起来。此外，我们证明了过表达的NF-κB在体内反激活E-选择蛋白启动子的能力取决于NF-ELAM1复合物。我们的结果表明，ATF和NF-κB之间的直接相互作用至少部分是这些因子特异性调节E-选择蛋白启动子活性的机制。

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