FUNCTIONAL CHARACTERIZATION OF THE POXVIRAL RING PROTEIN

痘病毒环蛋白的功能表征

• 批准号: 7715924
• 负责人: Klaus J Fruh
• 金额: $ 5.55万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715924
• 关键词: Affect; Apoptosis; Computer Retrieval of Information on Scientific Projects Database; Funding; Goals; Grant; In Vitro; Infection; Institution; Mediating; Molecular; Molecular Weight; Poxviridae; Proteins; Proteomics; Research; Research Personnel; Resources; Source; Testing; UV induced; Ubiquitin; Ubiquitin-Activating Enzymes; Ubiquitin-Conjugating Enzymes; Ubiquitination; United States National Institutes of Health; Viral; Virulence Factors; Virus; Virus Diseases; in vivo; macrophage; ubiquitin ligase

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to identify the molecular function of the poxviral virulence factor p28. P28 was shown to be an essential factor for controlling viral infection of macrophages and the inability to infect macrophages in vitro correlated with spontaneous clearance of infections in vivo. There is also some evidence that P28 protects against virally induced and UV-induced apoptosis. Specific aim 1 of this project is to test the hypothesis that p28 protects macrophages from apoptosis. We have recently demonstrated that P28 is a RING-domain ubiquitin ligase since P28 mediates the formation of high molecular weight ubiquitinated products in the presence of ubiquitin-conjugating enzymes, ubiquitin and the ubiquitin activating enzyme E1. In addition, we observed that ubiquitin is concentrated in poxvirus factories in the presence of P28 suggesting that P28 mediates the ubiquitination of viral and/or cellular proteins in virus factories. Therefore, Specific aim 2 is to use a proteomics approach to identify potential targets that are directly or indirectly affected by P28.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的目标是确定痘病毒毒力因子p28的分子功能。P28是控制病毒感染巨噬细胞的重要因素，体外感染巨噬细胞的能力与体内感染的自发清除有关。也有一些证据表明，P28对病毒诱导和紫外线诱导的细胞凋亡具有保护作用。这个项目的具体目标1是检验p28保护巨噬细胞免于凋亡的假设。我们最近证明了P28是一种环状结构的泛素连接酶，因为P28在泛素结合酶、泛素和泛素活化酶E1的存在下，介导了高分子量泛素产物的形成。此外，我们观察到泛素在P28存在的情况下集中在痘病毒工厂中，这表明P28介导了病毒工厂中病毒和/或细胞蛋白的泛素化。因此，特定的目标2是使用蛋白质组学的方法来确定直接或间接影响P28的潜在靶点。