Lack of responsiveness of a nuclear factor-kappaB-regulated promoter to transactivation by human immunodeficiency virus 1 Tat in HeLa cells.
Lack of responsiveness of a nuclear factor-kappaB-regulated promoter to transactivation by human immunodeficiency virus 1 Tat in HeLa cells.
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HeLa 细胞中核因子 kappaB 调节的启动子对人类免疫缺陷病毒 1 Tat 的反式激活缺乏反应性。
DOI：
10.1006/viro.1999.9966
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发表时间：
1999
期刊：
影响因子：
3.7
通讯作者：
Offermann,MK
中科院分区：
文献类型：
--
作者：
Kelly,GD;Morris,CB;Offermann,MK
Tat 蛋白的转录激活在很大程度上取决于与位于所有人类免疫缺陷病毒 1 型 (HIV-1) 转录物 5'-非翻译区的 TAR RNA 元件的相互作用。此外，Tat 已被证明可诱导核因子 κB (NF-κB) 的核转位，可能有助于基因诱导。 NF-κB 响应报告构建体 (PRDII)4-CAT 用于探索 Tat 激活的 NF-κB 产生的转录。 Tat 不激活 (PRDII)4-CAT，而 (PRDII)4-CAT 对转染的 Rel A 或肿瘤坏死因子-α (TNF-α) 高度敏感。尽管不能直接诱导，Tat 仍将 (PRDII)4-CAT 对转染的 Rel A 或 TNF-α 的反应性增强了约 2.5 倍。在没有转染的 Rel A 或外源 TNF-α 的情况下，含有 κB 和 TAR 元件的 HIV-LTR 衍生报告基因显示出高水平的 CAT 活性，并且在没有转染的 Rel A 或外源 TNF-α 的情况下，IκBα 的过表达抑制了 CAT 活性 60% 至 80%，这表明 Tat 对 NF-κB 的某些激活正在发生。当通过转染或通过 TNF-α 激活提供额外的 NF-κB 时，与单独使用 Tat 相比，HIV-LTR 报告基因活性增强了 3 至 6 倍。这些数据表明，Tat 无法激活一些 NF-κB 反应性启动子，但能够与 NF-κB 协同激活 HIV 衍生和非 HIV 衍生的启动子。
Transcriptional activation by Tat protein is in large part dependent on interactions with the TAR RNA element located in the 5′-untranslated region of all human immunodeficiency virus type 1 (HIV-1) transcripts. In addition, Tat has been shown to induce nuclear translocation of nuclear factor-κB (NF-κB), potentially contributing to gene induction. The NF-κB responsive reporter construct, (PRDII)4-CAT, was used to explore transcription resulting from NF-κB activated by Tat. Tat did not activate (PRDII)4-CAT, whereas (PRDII)4-CAT was highly responsive to either transfected Rel A or to tumor necrosis factor-α (TNF-α). Despite its inability to directly induce, Tat enhanced the responsiveness of (PRDII)4-CAT to either transfected Rel A or to TNF-α by ∼2.5-fold. High levels of CAT activity were seen with HIV-LTR-derived reporters that contained κB and TAR elements in response to transfected Tat in the absence of either transfected Rel A or exogenous TNF-α, and overexpression of IκBα with Tat inhibited CAT activity by 60% to 80%, suggesting that some activation of NF-κB by Tat was occurring. HIV-LTR reporter activities were enhanced three fold to sixfold compared with Tat alone when additional NF-κB was provided by transfection or by activation with TNF-α. These data indicate that Tat is unable to activate some NF-κB-responsive promoters but is able to synergize with NF-κB in the activation of both HIV-derived and non-HIV-derived promoters.