MECHANISMS OF GENE CONTROL BY THE VITAMIN D3 RECEPTOR

维生素 D3 受体的基因控制机制

• 批准号: 6649842
• 负责人: ROBERT P FISHER
• 金额: $ 29.14万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6649842
• 关键词: Baculoviridae; T lymphocyte; X ray crystallography; cell cycle proteins; cell differentiation; cell growth regulation; cholecalciferol; gene induction /repression; genetic promoter element; genetic transcription; hormone regulation /control mechanism; immunoprecipitation; interleukin 2; myeloid stem cell; nucleic acid sequence; oncoprotein p21; polymerase chain reaction; protein structure function; reporter genes; transcription factor; transfection /expression vector; vitamin D receptors; vitamin analog

DESCRIPTION: (Adapted from the applicant's abstract) The overall goal of this renewal application is to define the mechanism(s) of gene transcription by the vitamin D3 receptor (VDR). To do so, VDR will be described structurally in the context of its actions as both a transcriptional repressor and activator. The role of a newly discovered coactivator complex, called DRIP, that is recruited to nuclear receptors in a ligand-dependent manner and is required by VDR to elicit transcriptional activation at a promoter, will also defined functionally. The overall goals are to apply the information generated here to increase our knowledge of how nuclear receptors regulate gene transcription in response to hormones. The specific aims are: 1) To determine the structure of VDR in transactivating and transrepressing conformations; 2) To generate reagents required for the study of DRIP function in vivo and in vitro; 3) To define the mechanisms of VDR transactivation through coactivators, and 4) To define the mechanism of VDR-mediated coactivation on a complex promoter.

描述：（根据申请人的摘要进行了改编） 更新应用是为了确定基因转录的机制 维生素D3受体（VDR）。为此，VDR将在结构上描述 其动作作为转录阻遏物和激活因子的上下文。这 招募的新发现的共激活器复合物（称为Drip）的作用 以配体依赖性方式到核受体，VDR要求 引起启动子的转录激活也将定义 在功能上。总体目标是将此处生成的信息应用于 增加我们对核受体如何调节基因转录的了解 对激素的反应。具体目的是：1）确定 反式激活和反式构象的VDR； 2）生成 研究滴水功能在体内和体外所需的试剂； 3）到 通过共激活因子定义VDR反式激活的机制，4） 定义VDR介导的复合启动子上的共激活的机理。