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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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控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物化学研究相结合。目前的研究工作集中在理解逆转录病毒生命周期中的两个关键步骤：（1）逆转录病毒基因组通过逆转录酶复制和（2）未剪接的逆转录病毒转录本（包括组成性转运元件（CTE））的核输出。这些研究更一般地涉及（1）通过与相关聚合酶的比较分析来理解复制过程中重要的核酸相互作用，以及（2）mRNA的核输出，其由相同的宿主因子Tap介导。 Ape 1（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。 Ape 1的氧化还原功能涉及几种转录因子（包括c-Jun）的DNA结合结构域内的氧化半胱氨酸残基的还原。E3330是含有醌的小分子。它直接与Ape 1结合并抑制Ape 1的氧化还原功能。 E3330阻断Ape 1减少c-Jun的能力。