Human T‐cell leukemia virus type 1 Tax protein interacts with and mislocalizes the PDZ domain protein MAGI‐1
Human T‐cell leukemia virus type 1 Tax protein interacts with and mislocalizes the PDZ domain protein MAGI‐1
复制标题
人类 T 细胞白血病病毒 1 型 Tax 蛋白与 PDZ 结构域蛋白 MAGI-1 相互作用并使其错误定位
作者：
G. N. Makokha;Masahiko Takahashi;M. Higuchi;Suguru Saito;Yuetsu Tanaka;M. Fujii
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。HTLV-1编码癌蛋白Tax 1，其对于人T细胞的永生化和体内持续的HTLV-1感染是必需的。Tax 1在其C末端具有PDZ结合基序（PBM）。该基序对于Tax 1向T细胞系的转化活性和持续的HTLV-1感染至关重要。Tax 1通过PBM与PDZ结构域蛋白如Dlg 1和Scribble相互作用，但尚未确定哪些细胞PDZ蛋白介导Tax 1 PBM的功能。在这里，我们证明了Tax 1与PDZ结构域蛋白MAGI-1以PBM依赖性方式相互作用，并且这种相互作用将MAGI-1从293 T细胞和HTLV-1感染的T细胞中的去污剂可溶性细胞部分错误定位为去污剂不溶性细胞部分。此外，Tax 1-将T细胞系从白细胞介素（IL）-2-依赖性转化为IL-2-非依赖性生长选择了在mRNA水平上MAGI-1表达不可逆降低的细胞。这些发现意味着Tax 1与其他病毒癌蛋白一样，靶向MAGI-1，作为抑制其在HTLV-1感染细胞中的抗肿瘤功能的机制，有助于T细胞的转化活性和持续的HTLV-1感染。
Human T‐cell leukemia virus type 1 (HTLV‐1) is the etiological agent of adult T‐cell leukemia (ATL). HTLV‐1 encodes the oncoprotein Tax1, which is essential for immortalization of human T‐cells and persistent HTLV‐1 infection in vivo. Tax1 has a PDZ binding motif (PBM) at its C‐terminus. This motif is crucial for the transforming activity of Tax1 to a T‐cell line and persistent HTLV‐1 infection. Tax1 through the PBM interacts with PDZ domain proteins such as Dlg1 and Scribble, but it has not been determined yet, which cellular PDZ proteins mediate the functions of Tax1 PBM. Here we demonstrate that Tax1 interacts with the PDZ domain protein MAGI‐1 in a PBM‐dependent manner, and the interaction mislocalizes MAGI‐1 from the detergent‐soluble to the detergent‐insoluble cellular fraction in 293T cells and in HTLV‐1‐infected T‐cells. In addition, Tax1‐transformation of a T‐cell line from interleukin (IL)‐2‐dependent to IL‐2‐independent growth selects cells with irreversibly reduced expression of MAGI‐1 at mRNA level. These findings imply that Tax1, like other viral oncoproteins, targets MAGI‐1 as a mechanism to suppress its anti‐tumor functions in HTLV‐1‐infected cells to contribute to the transforming activity of T‐cells and persistent HTLV‐1 infection.
人类 T 细胞嗜淋巴细胞病毒 I 型基因组表达及其对神经退行性疾病和白血病期间细胞内信号通路的影响。
DOI：
10.2741/yao
发表时间：
2000
期刊：
Frontiers in bioscience : a journal and virtual library
影响因子：
--
作者：
Yao,J;Wigdahl,B
通讯作者：
Wigdahl,B
DOI：
10.1073/pnas.94.13.6670
发表时间：
1997-06-24
影响因子：
11.1
作者：
Le, SS;Weiss, RS;Javier, RT
通讯作者：
Javier, RT
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。
影响因子：
3.7
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
通讯作者：
Fujii,Masahiro