THYROID HORMONE RECEPTOR AND GENE EXPRESSION

甲状腺激素受体和基因表达

基本信息

  • 批准号:
    2016303
  • 负责人:
  • 金额:
    $ 12.74万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1988
  • 资助国家:
    美国
  • 起止时间:
    1988-07-01 至 1998-11-30
  • 项目状态:
    已结题

项目摘要

The long range goal of this research is to understand the molecular basis by which the nuclear thyroid hormone receptor (TR) mediates changes in specific gene transcription. TR binds to specific DNA sequences (thyroid hormone response elements or TREs) in both the absence and presence of hormone. Upon binding of hormone, TR undergoes a conformational change that converts it to a transcriptionally active state. The region of TR between the DNA-binding domain and the C-terminal end (residues 170 to 456 of the beta form) is responsible for ligand binding, dimerization and transcriptional activation. Little is currently known regarding these important processes. The focus of this proposal is to identify the critical amino acid residues responsible for these functions and to understand the mechanism of ligand-mediated transcriptional activation by TR. To accomplish these goals, we have established a yeast system in which expression of the reporter gene, beta-galactosidase, is under control of TR. Like many other mammalian transcription factors, TR can function in yeast to activate transcription provided an appropriate DNA recognition site is present. Using the yeast expression system, we have selected for mutations of the C-terminal region of TR that are defective in promoting transcriptional activation. These mutations fall into two general categories: those that fail to bind hormone and those that bind hormone normally, but cannot trans-activate. To evaluate the nature of these functional domains, we will further characterize the mutations leading to defects in hormone-binding and trans-activation. To identify amino acid residues that are in close contact with hormone, we will screen for mutations that alter the ligand-binding specificity of TR (Specific Aim #1). Mutations that bind hormone, but are defective in trans-activation, will be studied to determine whether the defects result from the failure of TR to undergo the ligand-mediated conformational change or lie directly within the trans-activation domain itself (Specific Aim #2). Recently, several laboratories have shown that TR binding and transcriptional activation on certain TREs can be enhanced by heterodimerization with the retinoid X receptor (RXR). We will use the mutations that we have isolated to study the roles of each of the receptor partners in the heterodimer in the activation process (Specific Aim #3). Finally, we will use phenotypic screening in yeast to identify regions of TR that are critical to the process of heterodimerization and to determine whether distinct dimerization domains are involved in interacting with different types of TREs (Specific Aim #4). These studies will allow a better understanding of the process of ligand-mediated transcriptional activation by TR and provide valuable tools for future work to further explore this process.
这项研究的长期目标是了解其分子基础

项目成果

期刊论文数量(0)
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专利数量(0)

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HOWARD C TOWLE其他文献

HOWARD C TOWLE的其他文献

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{{ truncateString('HOWARD C TOWLE', 18)}}的其他基金

Nutrient Control of Gene Expression & Cell Signaling
基因表达的营养控制
  • 批准号:
    7060812
  • 财政年份:
    2005
  • 资助金额:
    $ 12.74万
  • 项目类别:
Nutrient Control of Gene Expression & Cell Signaling
基因表达的营养控制
  • 批准号:
    6940522
  • 财政年份:
    2005
  • 资助金额:
    $ 12.74万
  • 项目类别:
THYROID HORMONE RECEPTOR AND GENE EXPRESSION
甲状腺激素受体和基因表达
  • 批准号:
    3240061
  • 财政年份:
    1988
  • 资助金额:
    $ 12.74万
  • 项目类别:
THYROID HORMONE RECEPTOR AND GENE EXPRESSION
甲状腺激素受体和基因表达
  • 批准号:
    3240063
  • 财政年份:
    1988
  • 资助金额:
    $ 12.74万
  • 项目类别:
THYROID HORMONE RECEPTOR AND GENE EXPRESSION
甲状腺激素受体和基因表达
  • 批准号:
    3240062
  • 财政年份:
    1988
  • 资助金额:
    $ 12.74万
  • 项目类别:
THYROID HORMONE RECEPTOR AND GENE EXPRESSION
甲状腺激素受体和基因表达
  • 批准号:
    3240058
  • 财政年份:
    1988
  • 资助金额:
    $ 12.74万
  • 项目类别:
THYROID HORMONE RECEPTOR AND GENE EXPRESSION
甲状腺激素受体和基因表达
  • 批准号:
    2141147
  • 财政年份:
    1988
  • 资助金额:
    $ 12.74万
  • 项目类别:
THYROID HORMONE RECEPTOR AND GENE EXPRESSION
甲状腺激素受体和基因表达
  • 批准号:
    3240060
  • 财政年份:
    1988
  • 资助金额:
    $ 12.74万
  • 项目类别:
THYROID HORMONE RECEPTOR AND GENE EXPRESSION
甲状腺激素受体和基因表达
  • 批准号:
    2608424
  • 财政年份:
    1988
  • 资助金额:
    $ 12.74万
  • 项目类别:
THYROID HORMONE RECEPTOR AND GENE EXPRESSION
甲状腺激素受体和基因表达
  • 批准号:
    2141148
  • 财政年份:
    1988
  • 资助金额:
    $ 12.74万
  • 项目类别:

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超生奥本海默化学中的化学结合理论及其在复杂分子系统中的应用
  • 批准号:
    20H00373
  • 财政年份:
    2020
  • 资助金额:
    $ 12.74万
  • 项目类别:
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