INTERACTIONS OF APE1 AND C-JUN WITH E3330

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 乔治亚迪斯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射线结晶学研究与互补的生化研究结合起来。目前的研究工作集中在从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)核输出非剪接逆转录病毒转录本，包括构成运输元件(CTE)。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在复制过程中重要的核酸相互作用，以及(2)由相同的宿主因子Tap介导的mRNA的核输出。APE1(APE(Delta)40)是一种参与氧化还原调节转录因子功能的蛋白。APE1的氧化还原功能包括还原几种转录因子DNA结合域中的氧化半胱氨酸残基，包括c-jun。E3330是一种含有苯二酚的小分子。它直接与APE1结合，抑制APE1的氧化还原功能。E3330阻断APE1降低c-jun的能力。

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.