INTERACTIONS OF APE1 AND C-JUN WITH E3330

APE1 和 C-JUN 与 E3330 的相互作用

• 批准号: 8361352
• 负责人: Millie M Georgiadis
• 金额: $ 4.9万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361352
• 关键词: Binding; Biochemical; Biological Process; Cysteine; DNA Binding Domain; Elements; Funding; Gene Expression Regulation; Genome; Grant; Integration Host Factors; JUN gene; Life Cycle Stages; Mass Spectrum Analysis; Mediating; Messenger RNA; National Center for Research Resources; Nuclear Export; Nucleic Acids; Oxidation-Reduction; Polymerase; Pongidae; Principal Investigator; Proteins; Quinones; RNA-Directed DNA Polymerase; Regulation; Research; Research Infrastructure; Resources; Roentgen Rays; Role; Source; Transcript; United States National Institutes of Health; biomedical resource; comparative; cost; human APEX1 protein; small molecule; transcription factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 Georgiadis实验室中的研究旨在了解蛋白质核酸相互作用在基因表达的复制，核输出和调节等基本生物学过程中的作用。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。当前的研究工作集中在原子细节上的理解上，在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，以及（2）核出口未叠加逆转录病毒转录物，包括组成型运输元件（CTE）。这些研究更普遍地与（1）通过与相关聚合酶进行比较分析和（2）mRNA的核酸分析在复制过程中对核酸相互作用的理解更加一般有关，mRNA的核出口是由相同的宿主因子介导的。 相关蛋白APE1（APE（Delta）40）是一种参与转录因子功能的氧化还原调节的蛋白质。 APE1的氧化还原函数涉及减少几种转录因子的DNA结合结构域中氧化的半胱氨酸残基，包括C-JUN。 E3330是一个含有醌的小分子。它直接与APE1结合并抑制APE1的氧化还原函数。 E3330阻止了APE1减少C-JUN的能力。