Human T-cell leukemia virus type 1 Tax oncoprotein induces and interacts with a multi-PDZ domain protein, MAGI-3.
Human T-cell leukemia virus type 1 Tax oncoprotein induces and interacts with a multi-PDZ domain protein, MAGI-3.
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人类 T 细胞白血病病毒 1 型 Tax 癌蛋白诱导多 PDZ 结构域蛋白 MAGI-3 并与之相互作用。
DOI：
10.1016/j.virol.2003.11.014
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发表时间：
2004
期刊：
影响因子：
3.7
通讯作者：
Fujii,Masahiro
中科院分区：
文献类型：
--
作者：
Ohashi,Minako;Sakurai,Mamoru;Higuchi,Masaya;Mori,Naoki;Fukushi,Masaya;Oie,Masayasu;Coffey,RobertJ;Yoshiura,Kenta;Tanaka,Yuetsu;Uchiyama,Makoto;Hatanaka,Masakazu;Fujii,Masahiro
人类T细胞白血病病毒1型（HTLV-1）是成人T细胞白血病（ATL）的病原体，而密切相关的病毒HTLV-2与此类恶性疾病无关。HTLV-1 Tax 1癌蛋白转化大鼠成纤维细胞系（Rat-1）的效率远高于HTLV-2 Tax 2。通过使用差异显示分析，我们分离MAGI-3作为Tax 1诱导基因在大鼠-1细胞。逆转录-聚合酶链反应（RT-PCR）分析证实Tax 1诱导Rat-1细胞中的MAGI-3。MAGI-3具有多个PDZ结构域，在293 T细胞中与Tax 1相互作用，但不与Tax 2相互作用。Tax 1与MAGI-3的相互作用依赖于PDZ结构域结合基序，这在Tax 2中缺失。Tax 1与MAGI-3的相互作用改变了它们各自的亚细胞定位，而且，这种相互作用与Tax 1在Rat-1细胞中相对于Tax 2的高转化活性密切相关。在HTLV-1感染的T细胞系中表达MAGI-3 mRNA和相关的MAGI-1，但不表达MAGI-2。我们的研究结果表明，Tax 1和MAGI-3的相互作用改变了它们各自的生物活性，这可能在Tax 1的转化以及HTLV-1相关疾病的发病机制中发挥作用。
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), whereas the closely related virus HTLV-2 has not been associated with such malignant conditions. HTLV-1 Tax1 oncoprotein transforms a rat fibroblast cell line (Rat-1) much more efficiently than does HTLV-2 Tax2. By using a differential display analysis, we isolated MAGI-3 as a Tax1-inducible gene in Rat-1 cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis confirmed that Tax1 induced MAGI-3 in Rat-1 cells. MAGI-3 has multiple PDZ domains and interacted with Tax1 but not Tax2 in 293T cells. The interaction of Tax1 with MAGI-3 was dependent on a PDZ domain-binding motif, which is missing in Tax2. The interaction of Tax1 with MAGI-3 altered their respective subcellular localization, and moreover, the interaction correlated well with the high transforming activities of Tax1 in Rat-1 cells relative to Tax2. MAGI-3 mRNA and the allied MAGI-1, but not MAGI-2, were expressed in HTLV-1-infected T-cell lines. Our results suggest that the interaction of Tax1 and MAGI-3 alters their respective biological activities, which may play a role in transformation by Tax1 as well as in the pathogenesis of HTLV-1-associated diseases.