Intracellular targeting of HIV Gag proteins
HIV Gag 蛋白的细胞内靶向
基本信息
- 批准号:6800266
- 负责人:
- 金额:$ 17.85万
- 依托单位:
- 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 2006-03-31
- 项目状态:已结题
- 来源:
- 关键词:SDS polyacrylamide gel electrophoresisbinding sitesconfocal scanning microscopycytoplasmflow cytometrygag proteingenetic translationhuman immunodeficiency virus 1intracellular transportmass spectrometrypolymerase chain reactionprotein localizationprotein protein interactionreporter genesribosomesvirus RNAvirus assemblyvirus replicationwestern blottingsyeast two hybrid system
项目摘要
DESCRIPTION (provided by applicant): The long-term goal of this project is obtain a more thorough understanding of how HIV Gag proteins are transported through the cell's cytoplasm and where they are directed. It is clear that cellular proteins are required for these processes. One such cellular protein found to interact with retroviral Gag proteins is Ubc9, a nuclear pore-associated E2 Sumo conjugating enzyme. The involvement of Ubc9 and sumoylation of HIV-1 Gag proteins will be investigated as to its relevance in HIV replication. The hypothesis proposed is that Ubc9 promotes the association between HIV Gag proteins and the nuclear compartment. Such an association may be essential for viral RNA packaging during virus assembly. Such a model would explain how Gag proteins are able to compete with ribosomes for viral RNA packaging or for translation. Alternatively Ubc9 may be important for the nuclear targeting of the pre-integration complex during the early stages of the viral life cycle. These ideas are based on the observations that many cellular proteins that sumoylated by Ubc9 are transported to the nuclear compartment. Secondly, over-expression of Ubc9 and Gag proteins results in a dramatic accumulation of Gag proteins either in or juxtaposed to the nuclear compartment. The studies proposed in this application focus on Ubc9-HIV interactions and the relevance of the interaction to HIV replication. We will characterize the interaction between Ubc9 and HIV proteins by identifying the interactions domains, by demonstrating that Ubc9 and HIV Gag co-localize in cells and by determining whether HIV Gag is sumoylated by Ubc9. Secondly, the biological significance of this interaction will be demonstrated by showing that an inability to interact with Ubc9 is lethal to the virus. The results obtained from these studies will provide important information about how Gag proteins function within cells and may provide a framework for developing novel therapeutic strategies to combat HIV replication.
描述(由申请人提供):该项目的长期目标是更彻底地了解HIV Gag蛋白如何通过细胞质运输以及它们的方向。很明显,这些过程需要细胞蛋白。其中一种与逆转录病毒Gag蛋白相互作用的细胞蛋白是Ubc9,一种核孔相关E2相扑结合酶。Ubc9的参与和HIV-1 Gag蛋白的聚合将被研究其在HIV复制中的相关性。提出的假设是Ubc9促进HIV Gag蛋白和核室之间的关联。在病毒组装过程中,这种关联可能是病毒RNA包装所必需的。这样的模型将解释Gag蛋白如何能够与核糖体竞争病毒RNA包装或翻译。另外,在病毒生命周期的早期阶段,Ubc9可能对整合前复合体的核靶向很重要。这些想法是基于观察到许多被Ubc9修饰的细胞蛋白被运送到核室。其次,Ubc9和Gag蛋白的过度表达导致Gag蛋白在核室内或并置的大量积累。本申请中提出的研究重点是Ubc9-HIV相互作用及其与HIV复制的相关性。我们将通过鉴定相互作用域、证明Ubc9和HIV Gag在细胞中共定位以及确定HIV Gag是否被Ubc9介导来表征Ubc9和HIV蛋白之间的相互作用。其次,这种相互作用的生物学意义将通过显示不能与Ubc9相互作用对病毒是致命的来证明。从这些研究中获得的结果将提供关于Gag蛋白如何在细胞内发挥作用的重要信息,并可能为开发对抗HIV复制的新治疗策略提供框架。
项目成果
期刊论文数量(0)
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ROBERT A WELDON其他文献
ROBERT A WELDON的其他文献
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{{ truncateString('ROBERT A WELDON', 18)}}的其他基金
HOST CELL CONTRIBUTIONS TO RETROVIRAL ASSEMBLY
宿主细胞对逆转录病毒组装的贡献
- 批准号:
7170371 - 财政年份:2005
- 资助金额:
$ 17.85万 - 项目类别:
HOST CELL CONTRIBUTIONS TO RETROVIRAL ASSEMBLY
宿主细胞对逆转录病毒组装的贡献
- 批准号:
7011812 - 财政年份:2004
- 资助金额:
$ 17.85万 - 项目类别:
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