ISOLATION AND CHARACTERIZATION OF PROGESTERONE RECEPTOR

孕酮受体的分离和表征

• 批准号: 6271993
• 负责人: DAVID O TOFT
• 金额: $ 15.95万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6271993
• 关键词: Saccharomyces cerevisiae; adenosine triphosphate; cell free system; chickens; gene deletion mutation; hormone binding protein; laboratory mouse; peptidylprolyl isomerase; progesterone receptors; protein structure function; receptor binding; reporter genes; reproductive hormone; reticulocytes; stress proteins

When in its inactive form in cytosol extracts, the avian progesterone receptor, like most steroid receptors, is complexed with the heat shock protein hsp90. This complex does not form through a simple association, but through a process that requires ATP hydrolysis and several additional proteins. other proteins in the receptor complex are hsp70 and three peptidylprolyl isomerases or immunophilins. Two of these, FKBP52 and FKBP54, bind the immunosuppressant drug FK506 and the third, CyP-40, binds cyclosporin A. A final protein in the receptor complex is p23 which is a unique phosphoprotein. We have made much progress in the description of receptor complexes and in the development of cell-free systems for their study. The objective of the proposed studies is to further our understanding on the assembly of receptor complexes, their dissociation upon hormone binding, and the functional significance of the receptor- associated proteins. This will be accomplished through the development and manipulation of chemically defined systems for receptor complex formation using purified proteins and specific antibody probes. Sub-complexes will also be analyzed to describe intermediates in complex formation and the various protein:protein interactions that occur. Finally, a yeast system with progesterone receptor will be used to identify the homologs of receptor-associated proteins in yeast and to test the biological significance of specific proteins of the complex by mutagenesis. These studies should provide new and valuable information on the earliest events in progesterone action and the axillary proteins that are needed for these events.

当在细胞质提取物中处于非活性形式时， 受体，像大多数类固醇受体，是复杂的热休克 hsp90蛋白。 这种复合体不是通过简单的联想形成的， 但是通过一个需要ATP水解和几个额外的 proteins. 受体复合物中的其它蛋白质是HSP 70和三种 肽基脯氨酰异构酶或亲免素。 其中两个，FKBP 52和 FKBP 54结合免疫抑制剂药物FK506，第三种CyP-40结合 环孢菌素A。 受体复合物中的最后一种蛋白质是p23， 独特的磷蛋白 我们在描述 受体复合物和无细胞系统的发展， study. 建议研究的目的，是进一步加强 了解受体复合物的组装、解离 以及受体的功能意义- 相关蛋白质 这将通过发展和 用于受体复合物形成的化学确定的系统的操作 使用纯化的蛋白质和特异性抗体探针。 子综合体将 也可以分析来描述络合物形成中的中间体， 各种蛋白质之间的相互作用。 最后，酵母系统 将用于鉴定孕酮受体的同源物， 酵母中的受体相关蛋白，并测试其生物学特性。 复合物的特异性蛋白质的突变的意义。 这些 这些研究应该提供关于最早期事件的新的和有价值的信息 孕酮的作用和这些作用所需的腋蛋白 事件