Enhanced activation of tax-dependent transcription of human T-cell leukemia virus type I (HTLV-I) long terminal repeat by TORC3
Enhanced activation of tax-dependent transcription of human T-cell leukemia virus type I (HTLV-I) long terminal repeat by TORC3
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DOI：
10.1074/jbc.m409021200
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发表时间：
2004-12-17
影响因子：
4.8
通讯作者：
Shimotohno, K
中科院分区：
文献类型：
--
作者：
Koga, H;Ohshima, T;Shimotohno, K
Tax是一种由人类T细胞白血病病毒I型(HTLV-I)env-px基因编码的蛋白，可与多种宿主细胞转录因子相互作用。TAX通过与环磷酸腺苷反应元件结合蛋白(CREB)结合，激活HTLV-I长末端重复序列(LTR)的转录。在这里，我们提出的证据是，CREB的共激活因子调节的环磷酸腺苷反应元件结合蛋白3(TORC3)的转导分子参与了税收诱导的HTLV-I LTR的转录激活。通过使用荧光素酶检测系统，我们表明TORC3单独可以促进HTLV-I LTR以及细胞环状AMP反应元件(CRE)的转录。有趣的是，我们发现TORC3和TAX的共表达显著增加了HTLV-I LTR的转录激活。我们还通过谷胱甘肽S转移酶下拉实验和免疫共沉淀实验证明了TORC3与Tax相互作用。通过缺失突变分析，我们确定TORC3的Tax相互作用结构域是一个从氨基酸1到103的区域，其中包含一个卷曲结构域。这些结果为理解税收依赖的HTLV-I转录激活的分子机制提供了重要线索。
Tax, a protein encoded by the env-pX gene of human T-cell leukemia virus type I (HTLV-I), interacts with various host cell transcription factors. Tax activates transcription from the long terminal repeat (LTR) of HTLV-I through association with cyclic AMP-responsive element-binding protein (CREB). Here, we present evidence that transducer of regulated cyclic AMP-response element-binding protein 3 (TORC3), a co-activator of CREB, is involved in Tax-induced transcriptional activation from the HTLV-I LTR. By using a luciferase assay system, we show that TORC3 alone can enhance transcription from the HTLV-I LTR, as well as from a cellular cyclic AMP-response element (CRE). Interestingly, we find that co-expression of TORC3 and Tax dramatically increased transcriptional activation at the HTLV-I LTR. We also show by glutathione S-transferase pull-down and co-immunoprecipitation experiments that TORC3 interacts with Tax. Using deletion mutant analysis, we identify the Tax interaction domain of TORC3 as a region spanning from amino acid 1 to 103, which contains a coiled-coil domain. These results provide important clues toward understanding the molecular mechanism of Tax-dependent transcriptional activation of the HTLV-I LTR.