TRANSFORMING GROWTH-FACTOR-BETA AND CYCLOSPORINE-A INHIBIT THE INDUCIBLE ACTIVITY OF THE INTERLEUKIN-2 GENE IN T-CELLS THROUGH A NONCANONICAL OCTAMER-BINDING SITE
TRANSFORMING GROWTH-FACTOR-BETA AND CYCLOSPORINE-A INHIBIT THE INDUCIBLE ACTIVITY OF THE INTERLEUKIN-2 GENE IN T-CELLS THROUGH A NONCANONICAL OCTAMER-BINDING SITE
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DOI：
10.1128/mcb.13.2.1155
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发表时间：
1993-02-01
影响因子：
5.3
通讯作者：
SERFLING, E
中科院分区：
文献类型：
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作者：
BRABLETZ, T;PFEUFFER, I;SERFLING, E
转化生长因子β（TGF-β）对免疫系统的许多不同细胞类型（包括T淋巴细胞）具有生长抑制作用。我们在这项研究中表明，TGF-β对T淋巴细胞的抑制作用是伴随着白细胞介素2（IL-2）基因表达的阻断，这是介导的，至少部分地，通过抑制IL-2启动子/增强子活性。IL-2增强子/启动子区的顺式调节（原增强子）元件的功能分析表明，大多数TGF-β反应元件映射到其所谓的上游启动子位点。上游启动子位点元件的原增强子活性也被环孢菌素A抑制。上游启动子位点DNA含有两个非典型的、紧密相连的八聚体和A.P-1样因子的结合序列。这两个位点都参与IL-2增强子活性的建立。由于真正的八聚体网站，但不是AP-1结合位点的活动也受到TGF-β和环孢菌素A在E14 T淋巴瘤细胞受损，我们得出结论，这两种免疫抑制剂干扰的活动，但不是在T淋巴细胞中的八聚体因子的DNA结合。
Transforming growth factor beta (TGF-beta) has a growth-inhibitory effect on numerous different cell types of the immune system, including T lymphocytes. We show in this study that the inhibitory action of TGF-beta on T lymphocytes is accompanied by a block of interleukin 2 (IL-2) gene expression which is mediated, at least in part, by inhibition of IL-2 promoter/enhancer activity. The functional analysis of cis-regulatory (proto-enhancer) elements of the IL-2 enhancer/promoter region showed that the most TGF-beta-responsive element maps to its so-called upstream promoter site. The proto-enhancer activity of the upstream promoter site element is also inhibited by cyclosporin A. The upstream promoter site DNA harbors two noncanonical, closely linked binding sequences for octamer and A.P-1-like factors. Both sites are involved in the establishment of IL-2 enhancer activity. Since the activity of genuine octamer sites but not that of AP-1-binding sites is also impaired by TGF-beta and cyclosporin A in El4 T lymphoma cells, we conclude that both immunosuppressives interfere with the activity but not the DNA binding of octamer factors in T lymphocytes.