权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Activation of the LMP-1 Protein of Epstein-Barr Virus

Epstein-Barr 病毒 LMP-1 蛋白的激活

基本信息

批准号：
7493926
负责人：
JENNIFER M MARTIN
金额：
$ 5.67万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7493926
关键词：
Address Area B lymphocyte immortalization B-Cell Lymphomas B-Lymphocytes Biochemical Biopsy C-terminal Cell Cycle Regulation Cell Line Cell Surface Receptors Cells Cities Colorado Complex Cytokinesis Data Depth Developmental Biology Doctor of Philosophy Face Goals Growth Human Human Herpesvirus 4 Human Resources In Vitro Individual Instruction Life Cycle Stages Light Link Malignant Neoplasms Mediating Membrane Membrane Microdomains Membrane Proteins Molecular Names Nasopharynx Carcinoma Numbers Oncogene Proteins Play Principal Investigator Printing Process Proteins Regulation Research Research Project Grants Role Signal Transduction Structure Testing Thinking Transmembrane Domain Tumor Cell Line Tumor Necrosis Factor Receptor Universities Work analog base cell growth cell growth regulation cell transformation design in vivo infected B cell insight lymphoblastoid cell line pathogen programs research study stoichiometry tumorigenesis

项目摘要

Epstein-Barr virus (EBV) is a human pathogen associated with a variety of cancers, including B cell lymphomas and nasopharyngeal carcinoma. EBV encodes an oncoprotein called the latent membrane protein-1 (LMP-1) whose activity is critical for B cell transformation by EBV. The ultimate goal of the proposed research is to explore the molecular and biochemical mechanisms by which LMP-1 contributes to EBV's life cycle in vitro and then to apply results to LMP-I's potential contribution to EBV's life cycle in vivo as it relates not only to the process of tumorigenesis but to the activity of EBV in latently infected B cells of healthy individuals. LMP-1 is expressed in infected primary B cells, immortalizaed lypmphoblastoid cell lines, and in some tumor cell lines or biopsies. LMP-1 functions as a constitutively-active cell surface receptor and activates positive growth- regulatory signals via its intracellular C-terminal signaling domain and negative growth-regulatory signals via its transmembrane domain. The studies described in this proposal are designed with the combined goals of understanding the function of LMP-I's hydrophobic transmembrane domain in the context of a) the mechanism of LMP-I's constitutive activation of cellular growth-regulatory signaling and b) signaling resulting in negative growth-regulation. Defining the mechanism of LMP- l's constitutive activation will provide insights into the control of cellular signal transduction and may be generally applicable to the molecular mechanisms involved in normal B cell growth control and in the aberrant growth of virally and nonvirally induced malignancies. Understanding the process of negative growth-regulation by LMP-1 will provide insights into the broad areas of cell cycle regulation and cytokinesis, and may shed light on the contribution of LMP-1 to EBV's life cycle in vivo, in transformed cells and in latently infected cells in healthy seropositive individuals. _ERP(JRMANGE S_TP--{S) {organization, city, state) >Department of Molecular, Cellular and Developmental Biology (MCDB), University of Colorado, Boulder KEY PERSONNEL. See instructions on Page 11. Use continuation pages as needed to provide the required information in the format shown below. Name Organization Role on Project Jennifer M. Martin, Ph.D. University of Colorado, MCDB Principal Investigator PHS 398 (Rev. 4/98) Page 2 E}B Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b. CC Principal Investigator/Program Director (Last, first, middle): > Martin_ Jennifer M. Type the name of the principal investigator/program director at the top of each printed page and each continuation page. (For type specifications, see instructions on page 6.) RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .......................................................................................................................................................................................................................... Description,

EB病毒（Epstein-Barr virus，EBV）是一种与多种癌症相关的人类病原体，包括B细胞淋巴瘤和鼻咽癌。EB病毒编码一种称为潜伏性膜蛋白-1（LMP-1），其活性对于EBV转化B细胞至关重要。的这项研究的最终目标是探索分子和生化机制， LMP-1对EBV体外生命周期的贡献，然后将结果应用于LMP-1的潜力，它不仅与肿瘤发生的过程有关，而且还与肿瘤细胞的增殖有关。 EBV在健康个体潜伏感染的B细胞中的活性。LMP-1在感染的原代B细胞、永生化的淋巴母细胞样细胞系以及一些肿瘤细胞系或活组织检查。 LMP-1作为一种组成型活性细胞表面受体发挥作用，并激活正性生长。通过其细胞内C-末端信号传导结构域和负生长调节信号通过其跨膜结构域传递信号。本提案中所述的研究是根据理解LMP-I的疏水跨膜结构域的功能， a）LMP-I对细胞生长调节的组成性激活的机制，信号传导和B）导致负生长调节的信号传导。定义LMP的机制- L的组成性激活将提供对细胞信号转导的控制的见解，可能普遍适用于涉及正常B细胞生长控制的分子机制以及病毒和非病毒诱导的恶性肿瘤的异常生长。了解 LMP-1的负生长调节过程将为细胞的广泛领域提供见解， LMP-1可能参与EBV的细胞周期调控和胞质分裂，并可能揭示LMP-1对EBV生命周期的贡献在健康血清反应阳性个体的转化细胞和潜伏感染细胞中进行。 _ERP（JRMANGE S_TP--{S）{组织、城市、州） >科罗拉多大学分子、细胞和发育生物学系，博尔德关键人员。参见第11页的说明。根据需要使用续页以如下所示的格式提供所需信息。名称组织在项目中的角色詹妮弗·M Martin博士科罗拉多大学MCDB首席研究员 PHS 398（Rev. 4/98）第2 E B页在整个应用程序的底部连续编号页面。不要使用后缀，如3a，3b。 CC首席研究员/项目总监（最后，第一，中间）：> Martin_ Jennifer M. 在各打印页和各续页的顶部键入主要研究者/项目负责人的姓名。(For型号规格，见说明书第6页）。研究资助目录页码首页.......................................................................................................................................................................................................................... 产品描述：