The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements.
The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements.
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人类免疫缺陷病毒 1 型长末端重复序列的 NF-kappa B 和 Sp1 基序充当新型甲状腺激素反应元件。
DOI：
10.1128/mcb.13.8.5057-5069.1993
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发表时间：
1993
影响因子：
5.3
通讯作者：
Samuels,HH
中科院分区：
文献类型：
--
作者：
Desai-Yajnik,V;Samuels,HH
我们报道甲状腺激素（T3）受体（T3 R）可以激活人类免疫缺陷病毒1型（HIV-1）长末端重复序列（LTR）。纯化的鸡T3 R-α1（cT 3 R-α1）作为单体和同源二聚体与LTR中含有两个串联NF-κB结合位点的区域（核苷酸-104至-75 [-104/-75]）和含有三个Sp1结合位点的区域（-80/-45）结合。相反，人视黄酸受体α（RAR-α）和小鼠类维生素A X受体β（RXR-β）不与这些元件结合。然而，RXR-β与cT 3R-α1结合为异二聚体，与RAR-α结合程度较低。凝胶迁移率变动分析也显示纯化的NF-κB p50/65或p50/50可以同时结合一个但不是两个NF-κB位点。尽管p50/65、p50/50和T3 R或Sp1和T3 R的结合位点重叠，但它们的结合是相互排斥的，并且在包含RXR-β的情况下，主要复合物是RXR-β-cT 3 R-α1异二聚体。当与异源启动子连接时，LTR的NF-κB区和来自κ轻链增强子的NF-κB元件都作为T3应答元件（TREs）起作用。HIV-1 NF-κB位点中的TREs似乎组织为半位点之间具有8或10 bp缺口的直接重复序列。消除cT 3 R-α1结合的NF-κB基序内的突变也消除了T3的刺激，表明cT 3 R-α1与Sp1区域的结合并不独立介导T3的激活。然而，Sp1区域被病毒达特因子转化为功能强大的TRE。这些研究表明，HIV-1 LTR含有tat依赖性和tat非依赖性TREs，并揭示了T3 R调节含有NF-κB样和Sp1样元件的其他基因的潜力。此外，它们表明其他转录因子在确定某些T3 R DNA结合序列是否可以作为活性TRE起作用中的重要性。
We report that thyroid hormone (T3) receptor (T3R) can activate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). Purified chick T3R-α1 (cT3R-α1) binds as monomers and homodimers to a region in the LTR (nucleotides -104 to -75 [-104/-75]) which contains two tandem NF-κB binding sites and to a region (-80/-45) which contains three Sp1 binding sites. In contrast, human retinoic acid receptor α (RAR-α) and mouse retinoid X receptor β (RXR-β) do not bind to these elements. However, RXR-β binds to these elements as heterodimers with cT3R-α1 and to a lesser extent with RAR-α. Gel mobility shift assays also revealed that purified NF-κB p50/65 or p50/50 can bind to one but not both NF-κB sites simultaneously. Although the binding sites for p50/65, p50/50, and T3R, or Sp1 and T3R, overlap, their binding is mutually exclusive, and with the inclusion of RXR-β, the major complex is the RXR-β-cT3R-α1 heterodimer. The NF-κB region of the LTR and the NF-κB elements from the κ light chain enhancer both function as T3 response elements (TREs) when linked to a heterologous promoter. The TREs in the HIV-1 NF-κB sites appear to be organized as a direct repeat with an 8- or 10-bp gap between the half-sites. Mutations within the NF-κB motifs which eliminate binding of cT3R-α1 also abolish stimulation by T3, indicating that cT3R-α1 binding to the Sp1 region does not independently mediate activation by T3. The Sp1 region, however, is converted to a functionally strong TRE by the viral tat factor. These studies indicate that the HIV-1 LTR contains both tat-dependent and tat-independent TREs and reveal the potential for T3R to modulate other genes containing NF-κB- and Sp1-like elements. Furthermore, they indicate the importance of other transcription factors in determining whether certain T3R DNA binding sequences can function as an active TRE.