Lowenthal J W, Ballard D W, Bogerd H, Böhnlein E, Greene W C
Howard Hughes Medical Institute, Department of Medicine, Durham, North Carolina 27710.
J Immunol. 1989 May 1;142(9):3121-8.
TNF-alpha induces the expression of IL-2R and promotes the proliferation and differentiation of T and B cells. In this report, we have studied the biochemical basis for TNF-alpha activation of the IL-2R alpha (Tac, p55) gene. Transfection of human T cell lines with selectively mutated forms of the IL-2R alpha promoter revealed that a kappa B element (nucleotides -267 to -256), as well as 5' flanking sequences (nucleotides -281 to -271) are required for TNF-alpha induction of this transcriptional unit. DNA binding studies demonstrated that this IL-2R alpha kappa B control element is specifically bound by a set of TNF-alpha inducible T cell nuclear proteins of relative Mr 80 to 90, 50 to 55, and 38 to 42 kDa. This protein recognition site from the IL-2R alpha promoter, as well as related kappa B motifs from the long terminal repeat of the type I human immunodeficiency virus, proved sufficient to impart TNF-alpha inducibility to an unresponsive heterologous promoter. These findings suggest that TNF-alpha-stimulated expression of the IL-2R alpha gene involves the induction of specific DNA binding proteins that in turn interact with a kappa B-like promoter element and facilitate activation of this transcription unit.
肿瘤坏死因子-α（TNF-α）可诱导白细胞介素-2受体（IL-2R）的表达，并促进T细胞和B细胞的增殖与分化。在本报告中，我们研究了TNF-α激活IL-2Rα（Tac，p55）基因的生化基础。用人T细胞系转染选择性突变形式的IL-2Rα启动子，结果显示κB元件（核苷酸-267至-256）以及5'侧翼序列（核苷酸-281至-271）是TNF-α诱导该转录单元所必需的。DNA结合研究表明，这个IL-2RακB控制元件特异性地与一组相对分子质量为80至90、50至55和38至42 kDa的TNF-α诱导的T细胞核蛋白结合。来自IL-2Rα启动子的这个蛋白质识别位点，以及来自I型人类免疫缺陷病毒长末端重复序列的相关κB基序，已证明足以赋予无反应的异源启动子TNF-α诱导性。这些发现提示，TNF-α刺激的IL-2Rα基因表达涉及诱导特定的DNA结合蛋白，这些蛋白继而与κB样启动子元件相互作用并促进该转录单元的激活。
