Alexandre C, Charnay P, Verrier B
Unité Mixte 103 CNRS-BioMérieux, Ecole Normale Supérieure de Lyon, France.
Oncogene. 1991 Oct;6(10):1851-7.
The HTLV-1 Tax protein has been shown to induce the expression of host cellular genes, some of which play crucial roles in cell proliferation and differentiation. We have examined the effect of Tax on the expression of two immediate-early genes, Krox-20 and Krox-24, which encode transcription factors. Several HTLV-1-infected T-cell lines and a HeLa cell line that constitutively expresses the Tax protein have a high level of expression of the Krox-20 and Krox-24 genes. In addition, Tax transactivates the promoters of both Krox-20 and Knox-24 in a co-transfection assay. Tax-responsive elements in Krox-20 and Krox-24 include the serum response elements (SREs) and the putative cAMP-responsive element (CRE). A correlation exists between the ability of these elements to mediate Tax transactivation and their affinity for their cognate factors, the serum response factor (SRF) or the CRE-binding protein (CREB) respectively. Since Tax is also able to transactivate the human c-fos promoter through the SRE and the CRE-60, our findings support the idea that the HTLV-1 Tax protein uses common mechanisms for transactivation of these three immediate-early genes. Deregulation of their expression may contribute to malignant transformation associated with HTLV-1 infection.
已证明人嗜T细胞病毒1型（HTLV-1）的Tax蛋白可诱导宿主细胞基因的表达，其中一些基因在细胞增殖和分化中起关键作用。我们研究了Tax对两个即早基因Krox-20和Krox-24表达的影响，这两个基因编码转录因子。几个感染了HTLV-1的T细胞系和一个组成性表达Tax蛋白的HeLa细胞系中，Krox-20和Krox-24基因表达水平很高。此外，在共转染实验中，Tax可反式激活Krox-20和Krox-24的启动子。Krox-20和Krox-24中的Tax反应元件包括血清反应元件（SREs）和假定的cAMP反应元件（CRE）。这些元件介导Tax反式激活的能力与其对同源因子（分别为血清反应因子（SRF）或CRE结合蛋白（CREB））的亲和力之间存在相关性。由于Tax还能够通过SRE和CRE-60反式激活人c-fos启动子，我们的研究结果支持这样一种观点，即HTLV-1 Tax蛋白利用共同机制反式激活这三个即早基因。它们表达的失调可能导致与HTLV-1感染相关的恶性转化。
