INTERACTIONS OF APE1 AND C-JUN WITH E3330

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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. 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.