Ballard D W, Böhnlein E, Lowenthal J W, Wano Y, Franza B R, Greene W C
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.
Science. 1988 Sep 23;241(4873):1652-5. doi: 10.1126/science.241.4873.1652.
Jurkat T cell lines constitutively expressing Tax, the 40-kilodalton transactivator protein of human T lymphotropic virus type I (HTLV-I), were used to investigate the mechanism by which this viral product deregulates the expression of the interleukin-2 receptor alpha gene (IL-2R alpha, Tac). Transfection of deleted forms of the IL-2R alpha promoter and in vitro DNA-binding studies revealed that a 12-base pair promoter segment, which has homology with the binding site for NF-kappa B, was required for Tax-induced activation of the IL-2R alpha promoter in vivo. An 18-base pair oligonucleotide containing this kappa B-like regulatory element proved sufficient to confer Tax inducibility upon a heterologous promoter. DNA affinity precipitation assays showed that Tax, like mitogenic stimuli, induced the expression of the 86-kilodalton cellular protein HIVEN86A, which specifically binds to the IL-2R alpha kappa B element in vitro. Furthermore, DNA/protein cross-linking studies revealed that several polypeptides interact with this sequence motif. Thus, the deregulation of IL-2R alpha gene expression encountered in HTLV-I leukemias appears to involve Tax activation of one or more cellular proteins that are normally induced by mitogens and that directly contribute to transcriptional activation of this receptor gene.
组成型表达Tax（人嗜T淋巴细胞病毒I型（HTLV-I）的40千道尔顿反式激活蛋白）的Jurkat T细胞系，被用于研究该病毒产物失调白细胞介素-2受体α基因（IL-2Rα，Tac）表达的机制。对IL-2Rα启动子缺失形式的转染及体外DNA结合研究表明，一个与NF-κB结合位点具有同源性的12碱基对启动子片段，是Tax在体内诱导激活IL-2Rα启动子所必需的。一个含有这种κB样调控元件的18碱基对寡核苷酸，被证明足以赋予异源启动子Tax诱导性。DNA亲和沉淀试验表明，Tax与促有丝分裂刺激一样，可诱导86千道尔顿细胞蛋白HIVEN86A的表达，该蛋白在体外可特异性结合IL-2Rα κB元件。此外，DNA/蛋白质交联研究显示，有几种多肽与该序列基序相互作用。因此，在HTLV-I白血病中遇到的IL-2Rα基因表达失调，似乎涉及Tax对一种或多种细胞蛋白的激活，这些蛋白通常由促有丝分裂原诱导产生，并直接促进该受体基因的转录激活。
