HUMAN B CELL TRANSFORMATION BY EPSTEIN BARR VIRUS

在这个项目中，调查者建议分析 EB病毒潜伏膜蛋白1(LMP-1)对细胞永生化的影响。 她将使用分子遗传和生化分析来确定 LMP-1的跨膜拓扑结构，研究LMP-1的四级结构 LMP-1及其与功能的相关性，并确定二者之间的关系 在LMP-1氨基末端的功能与其结构之间， 细胞骨架结合、周转和膜修补。具体的 本研究的目的是(1)确定细胞的跨膜拓扑结构 永生化细胞中的LMP-1蛋白，(2)确定同源基因是否为同源基因。 LMP-1的功能需要齐聚 永垂不朽，以及(3)确定 LMP-1胞质N末端与功能和生化的关系 细胞骨架结合、膜修补和快速的特性 周转率，所有这些都表明受体-配体的功能。这个 调查人员指出，虽然很明显，N端的 LMP-1负责EBV的转化，有争议的是 这是否仅仅是由于分子中的分子结构 膜，或由于蛋白质-蛋白质相互作用所致。最终， 研究人员希望确定LMP-1如何在信号中发挥作用 转导导致B细胞永生。

In this project, the investigator proposes to analyze the contribution of latent membrane protein 1 (LMP-1) of EBV to immortalization of cells. She will use molecular genetic and biochemical analyses to determine the transmembrane topology of LMP-1, to study the quaternary structure of LMP-1 and its relevance to function, and determine the relationship between the function of the amino -terminus of LMP-1 and its structure, cytoskeletal association, turnover, and membrane patching. The specific aims of the research are (1) to determine the transmembrane topology of the LMP-1 protein in the immortalized cell, (2) to determine if homo- oligomerization is required for function of the LMP-1 in immortalization, and (3) to determine how the structure of the cytoplasmic N-terminus of LMP-1 relates to function and the biochemical properties of cytoskeletal association, membrane patching, and rapid turnover, all of which suggest receptor-ligand function. The investigator points out that while it is clear that the N-terminal of LMP-1 is responsible for transformation by EBV, there is controversy as to whether this is due simply to the structure of the molecule in the membrane, or due to protein-protein interactions. Eventually, the investigator hopes to determine how LMP-1 functions in signal transduction leading to immortalization of B cells.