The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins
The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins
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DOI：
10.1038/sj.onc.1201567
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发表时间：
1998-02-05
期刊：
影响因子：
8
通讯作者：
Jalinot, P
中科院分区：
文献类型：
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作者：
Rousset, R;Fabre, S;Jalinot, P
HTLV-1感染与各种增生性或退行性疾病的出现有关。在表达Tax蛋白的转基因小鼠中观察到了其中一些疾病，已知Tax蛋白通过与几种转录因子相互作用反式激活各种病毒和细胞启动子。在这项研究中，我们发现这种病毒癌蛋白的C末端是一个基序，允许TAX与几种细胞蛋白的PDZ结构域结合。以Tax为诱饵的双杂交筛选确实产生了编码包括PDZ结构域在内的6种蛋白质的互补DNA。其中两个对应于截短形式的PSD-95和β1-合成素蛋白，另一个克隆编码的蛋白质与线虫基因LIN-7的产物同源。其他三个克隆编码PDZ细胞蛋白家族中的新人类成员。在哺乳动物细胞中的免疫沉淀分析证实了TAX与这些克隆产物的相互作用，对TAX的各种突变体的分析证实了C-末端氨基酸在其中几个相互作用中的重要性。这些数据表明，TAX可以通过与其PDZ结构域的强烈相互作用来扰乱靶细胞蛋白的正常功能。
Infection by HTLV-1 has been correlated with the appearance of various proliferative or degenerative diseases. Some of these disorders have been observed in transgenic mice expressing the Tax protein, which is known to transactivate various viral and cellular promoters through interactions with several transcription factors. In this study we show that the C-terminus of this viral oncoprotein represents a motif permitting binding of Tax to the PDZ domains of several cellular proteins. A two-hybrid screen with Tax as bait indeed yielded complementary DNAs coding for six proteins including PDZ domains. Two of them correspond to truncated forms of the PSD-95 and beta 1-syntrophin proteins, another clone codes for a protein homologous to the product of the C. elegans gene lin-7. The other three clones code for new human members of the PDZ family of cellular proteins. The interaction of Tax with the products of these clones was confirmed by immunoprecipitation assays in mammalian cells, and analysis of various mutants of Tax established the importance of the C-terminal amino acids for several of these interactions. These data suggest that Tax could perturb the normal function of targeted cellular proteins by strongly interacting with their PDZ domains.