HTLV-1交换激活器通过NF-kappa B类因子诱导介素-2受体表达
1Howard Hughes Medical Institute, University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor 48109.
Nature
|June 23, 1988
概括
人类T-淋巴细胞病毒-I (HTLV-I) 蛋白通过与NF-kappa B类转录因子相互作用,诱导介素-2受体α (IL-2Rα) 的表达. 这种相互作用类似于人类免疫缺陷病毒-1 (HIV-1) 如何使用NF-kappa B.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 人类T淋巴细胞病毒-I (HTLV-I) 感染灵长类细胞并刺激宿主蛋白质的产生.
- 感染HTLV-I的T细胞合成了IL-2Rα链,可能由病毒tat-I基因产物介导.
- 激活的T细胞利用转录因子NF-kappa B通过特定的增强剂序列来增强人类免疫缺陷病毒-1 (HIV-1) 的表达.
研究的目的:
- 研究HTLV-I tat-I基因产物诱导IL-2Rαα表达的机制.
- 为了确定类似于NF-kappa B的转录因子是否参与HTLV-I tat-I介导的IL-2Rα诱导.
- 确定负责IL-2Rα基因表达中的tat-I反应的特定DNA序列.
主要方法:
- 序列分析以确定IL-2Rα基因上游的潜在调节元素.
- 电泳运动转移试验用于评估转录因子与确定序列的结合.
- 记者基因测试使用异质促进子,并插入识别序列的副本来测试tat-I响应性.
主要成果:
- 确定了IL-2Rα的上游序列,与NF-kappa B结合部位 (kappa B) 具有显著的同质性.
- 这种已识别的序列竞争着与kappa B位点的结合,并在促进器的上游多元化时作为tat-I响应元件起作用.
- 据证明,tat-I产品在转染细胞中诱导了kappa B结合活性和IL-2Rα kappa B结合活性.
结论:
- HTLV-I tat-I 与NF-kappa B类转录因子相互作用,诱导IL-2Rαα表达.
- 无论是HTLV-I还是HIV-1,都使用类似的转录因子通路,涉及NF-kappa B型因子.
- 这些发现表明NF-kappa B类因子在病毒感染期间调节生长因子受体基因表达中的潜在作用.
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