The RAN GTPase

RAN GTP 酶

• 批准号: 7072315
• 负责人: IAN G MACARA
• 金额: $ 30.35万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7072315
• 关键词: RNA binding protein; cell cycle; cell cycle proteins; clinical research; computational biology; double stranded RNA; fluorescence resonance energy transfer; guanosinetriphosphatases; immunoprecipitation; laboratory mouse; mass spectrometry; nuclear membrane; nucleoproteins; protein binding; protein structure function; protein transport; tissue /cell culture; transcription factor; transport proteins

DESCRIPTION (provided by applicant): The continuing goal of this grant is to understand at a molecular level the functions of the Ran GTPase, and of Ran-interacting proteins, in nuclear import and export. Substantial progress was made within the previous funding period to determine how the RanGTP gradient across the nuclear envelope is formed, to identify a new class of transport cofactors, and discover novel transport carriers. The following specific aims will build on these advances: 1. A combination of computational biology and experimental tests will be used to evaluate different protein import mechanisms, and to determine the rate-limiting steps in import, using intact cells under physiologically relevant conditions. 2. The roles of exportin-5 and of ILF3/NFAR in dsRNA binding and export will be elucidated. 3. The hypothesis will be tested that the transport cofactors RanBP3 and Npap60 function in cargo selection and nuclear pore association to regulate protein export and import. Nucleo-cytoplasmic transport is central to the function of the eukaryotic cell, and is a key regulatory step in signal transduction pathways that modulate gene expression and the cell cycle. Nuclear import and export are also critical to the life cycles of many pathogenic viruses, and nuclear transport pathways are frequently subverted by these agents to ensure preferential replication of the viral genome, and to inactivate anti-viral defense mechanisms. Understanding the mechanisms of nuclear transport at a molecular level may therefore provide important new targets for anti-viral therapies.

描述（由申请人提供）：这项资助的持续目标是在分子水平上了解 Ran GTP 酶和 Ran 相互作用蛋白在核进出口中的功能。在上一个资助期内，我们在确定跨核膜的 RanGTP 梯度如何形成、识别一类新的转运辅助因子以及发现新型转运载体方面取得了实质性进展。以下具体目标将建立在这些进展的基础上： 1. 将使用计算生物学和实验测试相结合来评估不同的蛋白质导入机制，并在生理相关条件下使用完整细胞来确定导入的限速步骤。 2. 将阐明exportin-5 和ILF3/NFAR 在dsRNA 结合和输出中的作用。 3. 将检验运输辅助因子 RanBP3 和 Npap60 在货物选择和核孔关联中发挥作用以调节蛋白质输出和输入的假设。核质转运是真核细胞功能的核心，是调节基因表达和细胞周期的信号转导途径的关键调节步骤。核输入和输出对于许多病原病毒的生命周期也至关重要，这些物质经常破坏核运输途径，以确保病毒基因组的优先复制，并使抗病毒防御机制失活。因此，在分子水平上了解核转运机制可能为抗病毒治疗提供重要的新靶点。