Activation of the IL-2 gene promoter by HTLV-I Tax involves induction of NF-AT complexes bound to the CD28-responsive element
Activation of the IL-2 gene promoter by HTLV-I Tax involves induction of NF-AT complexes bound to the CD28-responsive element
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DOI：
10.1002/j.1460-2075.1996.tb00744.x
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发表时间：
1996-07-15
期刊：
影响因子：
11.4
通讯作者：
Sun, SC
中科院分区：
文献类型：
--
作者：
Good, LF;Maggirwar, SB;Sun, SC
I 型人类 T 细胞白血病病毒 (HTLV-I) 的 Tax 基因产物是多种生长相关细胞基因的有效转录激活剂，包括编码白细胞介素 2 (IL-2) 的基因。许多这些靶基因的税务激活似乎是由细胞转录因子 NF-kappa B/Rel 和 CREB/ATF 家族介导的。然而，Tax 反式激活 IL-2 基因的机制仍不清楚。在本研究中，我们证明 NF-kappa B/Rel 和 CREB/ATF 都不足以 TAX 介导的 IL-2 启动子激活。两种新型核蛋白复合物由 Tax 诱导，并特异性结合 IL-2 基因增强子，即 CD28 响应元件 (CD28RE)。免疫生化分析表明，这些 DNA 结合复合物至少含有活化 T 细胞核因子的两个成员：NF-ATp 和 NF-ATc。然而，CD28 结合 NF-AT 复合物不包含 Jun 和 Fos 家族蛋白，这些蛋白已被提议作为 NF-AT 伴侣参与 IL-2 NF-AT 基序的激活。瞬时转染研究表明，体内表达的 NF-ATp 与 CD28RE 探针结合，增强了 Tax 介导的这一关键 IL-2 增强子的激活。我们进一步证明 NF-AT 与 CD28RE 的结合对于 IL-2 启动子的 Tax 激活至关重要。总之，这些结果表明了一种 Tax 介导的 IL-2 基因激活的新机制，其中涉及诱导含有 NF-AT 的 CD28RE 结合复合物。
The tax gene product of the type I human T-cell leukemia virus (HTLV-I) is a potent transcriptional activator of various growth-related cellular genes, including that encoding interleukin-2 (IL-2). Tax activation of many of these target genes appears to be mediated by the NF-kappa B/Rel and CREB/ATF family of cellular transcription factors. However, the mechanism by which Tax transactivates the IL-2 gene remains unclear. In the present study, we demonstrate that neither NF-kappa B/Rel nor CREB/ATF is sufficient for Tax-mediated activation of the IL-2 promoter. Two novel nuclear protein complexes are induced by Tax and specifically bind to an IL-2 gene enhancer, the CD28-responsive element (CD28RE). Immunobiochemical analyses suggest that these DNA binding complexes contain at least two members of the nuclear factor of activated T cells, NF-ATp and NF-ATc. However, the CD28 binding NF-AT complexes do not contain Jun and Fos family proteins that have been proposed to serve as NF-AT partners in the activation of the IL-2 NF-AT motif. Transient transfection studies demonstrate that the in vivo expressed NF-ATp binds to the CD28RE probe and enhances Tax-mediated activation of this critical IL-2 enhancer. We demonstrate further that binding of NF-AT to CD28RE is critical for Tax activation of the IL-2 promoter. Together, these results suggest a novel mechanism of Tax-mediated activation of the IL-2 gene, which involves the induction of NF-AT-containing CD28RE binding complexes.