Functionally distinct monomers and trimers produced by a viral oncoprotein
Functionally distinct monomers and trimers produced by a viral oncoprotein
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DOI：
10.1038/sj.onc.1210784
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发表时间：
2008-02-28
期刊：
影响因子：
8
通讯作者：
Javier, R. T.
中科院分区：
文献类型：
--
作者：
Chung, S-H;Weiss, R. S.;Javier, R. T.
虽然同源寡聚体形成和分解成亚基的过程代表了调节蛋白质活性的常见策略，但其中亚基和同源寡聚体执行独立功能的蛋白质的报道很少。腺病毒E4-ORF 1癌蛋白诱导的肿瘤发生依赖于其与选定的一组细胞PDZ蛋白的结合，包括MUPP 1、MAGI-1、ZO-2和Dlg 1。我们在这里报道，在细胞中E4-ORF 1以单体和三聚体的形式存在，单体特异性地结合并隔离不溶性复合物内的MUPP 1、MAGI-1和ZO-2，而三聚体特异性地结合Dlg 1并促进其易位至质膜。这项工作揭示了一种新的策略，其中蛋白质的寡聚化状态不仅决定了结合单独相关靶标的能力，而且还将相互作用与不同的功能后果相结合。
While the process of homo-oligomer formation and disassembly into subunits represents a common strategy to regulate protein activity, reports of proteins in which the subunit and homo-oligomer perform independent functions are scarce. Tumorigenesis induced by the adenovirus E4-ORF1 oncoprotein depends on its binding to a select group of cellular PDZ proteins, including MUPP1, MAGI-1, ZO-2 and Dlg1. We report here that in cells E4-ORF1 exists as both a monomer and trimer and that monomers specifically bind and sequester MUPP1, MAGI-1 and ZO-2 within insoluble complexes whereas trimers specifically bind Dlg1 and promote its translocation to the plasma membrane. This work exposes a novel strategy wherein the oligomerization state of a protein not only determines the capacity to bind separate related targets but also couples the interactions to different functional consequences.