Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein
Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein
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DOI：
10.1073/pnas.94.13.6670
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发表时间：
1997-06-24
影响因子：
11.1
通讯作者：
Javier, RT
中科院分区：
文献类型：
--
作者：
Le, SS;Weiss, RS;Javier, RT
9ORF1 基因编码腺病毒 E4 区癌蛋白，其转化活性需要 C 端区域。使用 9ORF1 蛋白探针筛选 lambda gt11 cDNA 表达文库，产生了一种新的含有 PDZ 结构域的细胞蛋白 9BP-1，该蛋白后缀为野生型，但不是转化缺陷的 C 端突变型 9ORF1 蛋白。PDZ 结构域与某些蛋白自由 C 端的特定序列复合的事实导致人们认识到 9ORF1 C 端区域包含这样一个共有结合基序，这一发现促进了研究研究9ORF1蛋白是否与具有PDZ结构域的其他细胞蛋白结合，众所周知，9ORF1蛋白在体外和体内与含有PDZ结构域的蛋白hDlg/SAP97 (DLG)直接相互作用，hDlg/SAP97是果蝇盘大肿瘤抑制蛋白的哺乳动物同源物，并且还结合腺瘤性息肉病大肠杆菌肿瘤抑制蛋白，令人感兴趣的是，在形成复合物时，9ORF1蛋白优先与 DLG 的第二个 PDZ 结构域相关，类似于腺瘤性息肉病大肠杆菌蛋白。人 T 细胞白血病病毒 1 型 Tax 和大多数致癌人乳头瘤病毒 E6 癌蛋白在其 C 末端也具有 PDZ 结构域结合基序，并且值得注意的是，人 T 细胞白血病病毒 1 型 Tax 和人乳头瘤病毒 18 E6 蛋白在体外结合 DLG。考虑到转化中 9ORF1 C 端区域的要求，这些发现表明，与细胞因子 DLG 的相互作用可能有助于多种细胞的致瘤潜力。不同的人类病毒癌蛋白。
The 9ORF1 gene encodes an adenovirus E4 region oncoprotein that requires a C-terminal region for transforming activity. Screening a lambda gt11 cDNA expression library with a 9ORF1 protein probe yielded a novel cellular PDZ domain-containing protein, 9BP-1, which hinds to wild-type, bur not a transformation-defective, C-terminal, mutant 9ORF1 protein, The fact that PDZ domains complex with specific sequences at the free C-terminal end of some proteins led to the recognition that the 9ORF1 C-terminal region contained such a consensus-binding motif, This discovery prompted investigations into whether the 9ORF1 protein associates with additional cellular proteins having PDZ domains, It was round that the 9ORF1 protein interacts directly, in vitro and itt vivo, with the PDZ domain-containing protein hDlg/SAP97 (DLG), which is a mammalian homolog of the Drosophila discs large tumor suppressor protein and which also binds the adenomatous polyposis coli tumor suppressor protein, Of interest, in forming complexes, the 9ORF1 protein preferentially associated with the second PDZ domain of DLG, similar to adenomatous polyposis coli protein. Human T cell leukemia virus type 1 Tax and most oncogenic human papillomavirus E6 oncoproteins also possessed PDZ domain-binding motifs at their C termini and, significantly, human T cell leukemia virus type 1 Tax and human papillomavirus 18 E6 proteins bound DLG in vitro, Considering the requirement of the 9ORF1 C-terminal region in transformation, these findings suggest that interactions with the cellular factor DLG may contribute to the tumorigenic potentials of several different human virus oncoproteins.