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首页> 外文期刊>Molecular and Cellular Biology >Molecular Interactions Involved in the Transactivation of the Human T-Cell Leukemia Virus Type 1 Promoter Mediated by Tax and CREB-2 (ATF-4)
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Molecular Interactions Involved in the Transactivation of the Human T-Cell Leukemia Virus Type 1 Promoter Mediated by Tax and CREB-2 (ATF-4)

机译:税收和CREB-2(ATF-4)介导的人类T细胞白血病病毒1型启动子反式激活的分子相互作用。

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The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates viral transcription through three 21-bp repeats located in the U3 region of the HTLV-1 long terminal repeat and called Tax-responsive elements (TxREs). Each TxRE contains nucleotide sequences corresponding to imperfect cyclic AMP response elements (CRE). In this study, we demonstrate that the bZIP transcriptional factor CREB-2 is able to bind in vitro to the TxREs and that CREB-2 binding to each of the 21-bp motifs is enhanced by Tax. We also demonstrate that Tax can weakly interact with CREB-2 bound to a cellular palindromic CRE motif such as that found in the somatostatin promoter. Mutagenesis of Tax and CREB-2 demonstrates that both N- and C-terminal domains of Tax and the C-terminal region of CREB-2 are required for direct interaction between the two proteins. In addition, the Tax mutant M47, defective for HTLV-1 activation, is unable to form in vitro a ternary complex with CREB-2 and TxRE. In agreement with recent results suggesting that Tax can recruit the coactivator CREB-binding protein (CBP) on the HTLV-1 promoter, we provide evidence that Tax, CREB-2, and CBP are capable of cooperating to stimulate viral transcription. Taken together, our data highlight the major role played by CREB-2 in Tax-mediated transactivation.
机译:人类T细胞白血病病毒1型(HTLV-1)Tax蛋白通过位于HTLV-1长末端重复序列U3区的三个21 bp重复序列激活病毒转录,这种重复序列称为Tax-应答元件(TxRE)。每个TxRE包含对应于不完整的环状AMP反应元件(CRE)的核苷酸序列。在这项研究中,我们证明了bZIP转录因子CREB-2能够在体外与TxRE结合,并且CREB-2与每个21 bp的基序结合均通过Tax得以增强。我们还证明,Tax可以与CREB-2弱相互作用,而CREB-2则与诸如生长抑素启动子中的细胞回文CRE基序结合。 Tax和CREB-2的诱变表明,这两种蛋白之间的直接相互作用需要Tax的N和C端结构域以及CREB-2的C端区域。此外,对HTLV-1活化有缺陷的Tax突变体M47无法在体外与CREB-2和TxRE形成三元复合物。与最近的结果表明Tax可以在HTLV-1启动子上募集共激活剂CREB结合蛋白(CBP)一致,我们提供了Tax,CREB-2和CBP能够协同刺激病毒转录的证据。综上所述,我们的数据强调了CREB-2在税收介导的反式激活中所起的主要作用。

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