INTERACTIONS OF APE1 AND C-JUN WITH E3330

APE1 和 C-JUN 与 E3330 的相互作用

• 批准号: 7721477
• 负责人: Millie M Georgiadis
• 金额: $ 0.05万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721477
• 关键词: Binding; Biochemical; Biological Process; Computer Retrieval of Information on Scientific Projects Database; Cysteine; DNA Binding Domain; E 3330; Elements; Funding; Gene Expression Regulation; Genome; Grant; Institution; Integration Host Factors; JUN gene; Life Cycle Stages; Mediating; Nuclear Export; Nucleic Acids; Oxidation-Reduction; Polymerase; Pongidae; Proteins; Quinones; RNA-Directed DNA Polymerase; Regulation; Research; Research Personnel; Resources; Roentgen Rays; Role; Source; Transcript; United States National Institutes of Health; benzoquinone; comparative; human APEX1 protein; mRNA Export; small molecule; transcription factor

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. Research in the Georgiadis lab is directed toward understanding the role of protein-nucleic acid interactions in such fundamental biological processes as replication, nuclear export, and regulation of gene expression. Our approach is to integrate X-ray crystallographic studies with complementary biochemical studies. Current research efforts are focused on understanding in atomic detail two critical steps in the retroviral life cycle: (1) replication of the retroviral genome by reverse transcriptase and (2) nuclear export of unspliced retroviral transcripts including the constitutive transport element (CTE). These studies are related more generally to (1) the understanding of nucleic acid interactions that are important during replication through comparative analysis with related polymerases and (2) nuclear export of mRNA, which is mediated by the same host factor, Tap. A related protein, Ape1 (Ape(delta)40) is a protein that participates in redox regulation of transcription factor function. The redox function of Ape1 involves reduction of oxidized cysteine residues within the DNA binding domains of several transcription factors, including c-Jun. E3330 is a small molecule containing a quinone. It binds directly to Ape1 and inhibits the redox function of Ape1. E3330 blocks the ability of Ape1 to reduce c-Jun.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 Georgiadis 实验室的研究旨在了解蛋白质-核酸相互作用在复制、核输出和基因表达调节等基本生物过程中的作用。我们的方法是将 X 射线晶体学研究与互补的生化研究相结合。目前的研究工作集中在原子细节上了解逆转录病毒生命周期中的两个关键步骤：（1）通过逆转录酶复制逆转录病毒基因组；（2）包括组成型转运元件（CTE）在内的未剪接逆转录病毒转录本的核输出。这些研究更广泛地涉及（1）通过与相关聚合酶的比较分析来了解复制过程中重要的核酸相互作用，以及（2）mRNA 的核输出，这是由相同的宿主因子 Tap 介导的。 相关蛋白 Ape1 (Ape(delta)40) 是一种参与转录因子功能氧化还原调节的蛋白。 Ape1 的氧化还原功能涉及多种转录因子（包括 c-Jun）DNA 结合域内氧化半胱氨酸残基的还原。 E3330是一种含有醌的小分子。它直接与 Ape1 结合并抑制 Ape1 的氧化还原功能。 E3330 阻断 Ape1 还原 c-Jun 的能力。