E6 Interaction with Cellular PDZ Proteins

描述(由申请人提供)：来自癌症相关人乳头瘤病毒(HPV)的E6癌蛋白与含有PDZ基序的细胞蛋白的子集相关联。遗传证据表明，E6与细胞内PDZ蛋白的相互作用是HPV病毒在人角质形成细胞中完全复制和在小鼠鳞状细胞中转化表型所必需的。由于几种不同的细胞蛋白复合体通过PDZ相互作用与E6相互作用，特定的PDZ含有E6靶标的意义尚未确定。我们使用蛋白质组学的方法来鉴定与癌症相关的E6癌蛋白相互作用的细胞蛋白的复合体。这发现了通过PDZ配体相互作用与E6相互作用的新型细胞蛋白复合体。这项应用的目的是表征我们所鉴定的PDZ复合体，并探索E6-PDZ蛋白相互作用的生物学意义。

DESCRIPTION (provided by applicant): E6 oncoproteins from cancer associated Human Papillomaviruses (HPV) associate with a subset of cellular proteins that contain PDZ motifs. Genetic evidence has shown that the interaction of E6 with cellular PDZ proteins is necessary for both full HPV virus replication in human keratinocytes and transformed phenotypes in mouse squamous cells. As several different complexes of cellular proteins interact with E6 via PDZ interactions, the significance of particular PDZ containing targets of E6 is not defined. We have used a proteomics approach to identify complexes of cellular proteins that interact with cancer associated E6 oncoproteins. This has identified novel complexes of cellular proteins that interact with E6 by PDZ ligand interactions. The purpose of this application is to characterize the PDZ complexes we have identified, and to explore the biological significance of E6-PDZ protein interactions.