Chung S-H, Weiss R S, Frese K K, Prasad B V V, Javier R T
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Oncogene. 2008 Feb 28;27(10):1412-20. doi: 10.1038/sj.onc.1210784. Epub 2007 Sep 10.
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.
虽然同型寡聚体形成并分解为亚基的过程是调节蛋白质活性的常见策略，但亚基和同型寡聚体执行独立功能的蛋白质报道却很少见。腺病毒E4-ORF1癌蛋白诱导的肿瘤发生取决于它与一组特定的细胞PDZ蛋白的结合，包括MUPP1、MAGI-1、ZO-2和Dlg1。我们在此报告，在细胞中E4-ORF1以单体和三聚体形式存在，单体特异性结合并将MUPP1、MAGI-1和ZO-2隔离在不溶性复合物中，而三聚体特异性结合Dlg1并促进其向质膜转位。这项工作揭示了一种新策略，即蛋白质的寡聚化状态不仅决定了结合不同相关靶标的能力，还将相互作用与不同的功能后果联系起来。
