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首页> 外文期刊>Molecular and Cellular Biology >A cis element required for induction of the interleukin 2 enhancer by human T-cell leukemia virus type I binds a novel Tax-inducible nuclear protein.
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A cis element required for induction of the interleukin 2 enhancer by human T-cell leukemia virus type I binds a novel Tax-inducible nuclear protein.

机译：I型人T细胞白血病病毒诱导白介素2增强子所需的顺式元素与新型的Tax诱导型核蛋白结合。

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摘要

The 40-kDa nuclear protein Tax encoded by human T-cell leukemia virus type I (HTLV-I) can transcriptionally activate the interleukin 2 (IL-2) enhancer even in the presence of the immunosuppressant cyclosporin A, which inhibits the activation of the IL-2 enhancer by T-cell mitogens. We have identified a Tax-responsive element (TxRE) from -164 to -145 bp in the IL-2 enhancer which is sufficient to confer Tax responsiveness. A 45-kDa nuclear protein (TxRE-binding factor [TxREF]), present in Tax-expressing Jurkat cell lines but not in Jurkat cells without Tax, specifically interacts with the 5' TxRE sequence from -164 to -154. Deletion or mutation of this 5' TxRE sequence removes the binding of TxREF in vitro and dramatically reduces Tax activity in vivo. In addition, this site is responsible for the cyclosporin A-resistant expression of the IL-2 enhancer in the presence of Tax. Although the TxREF binding site contains an NF-kappa B like motif, UV cross-linking studies as well as gel retardation analysis reveal that TxREF is distinct from NF-kappa B. These results demonstrate that TxREF is a novel Tax-inducible DNA-binding protein and that TxRE plays a crucial role in mediating Tax-induced IL-2 gene expression.
机译：I型人T细胞白血病病毒（HTLV-1）编码的40 kDa核蛋白Tax即使在存在免疫抑制剂环孢菌素A的情况下也可以转录激活白介素2（IL-2）增强子，从而抑制了白细胞介素2的激活。 T细胞促细胞分裂剂产生IL-2增强剂。我们已经在IL-2增强子中从-164到-145 bp鉴定了一个税收响应元件（TxRE），足以赋予税收响应能力。存在于表达Tax的Jurkat细胞系中而不存在于没有Tax的Jurkat细胞中的45 kDa核蛋白（TxRE结合因子[TxREF]）与-164至-154的5'TxRE序列特异性相互作用。该5'TxRE序列的缺失或突变在体外去除了TxREF的结合，并显着降低了体内的Tax活性。另外，该位点负责在存在Tax的情况下IL-2增强子对环孢菌素A的抗性表达。尽管TxREF结合位点包含类似NF-κB的基序，但UV交联研究和凝胶阻滞分析显示TxREF与NF-κB截然不同。这些结果表明TxREF是一种新型的税务诱导DNA结合蛋白和TxRE在介导Tax诱导的IL-2基因表达中起关键作用。

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