PULMONARY DEVELOPMENT: Molecular and Cellular Analysis

肺部发育：分子和细胞分析

• 批准号: 7325665
• 负责人: Parviz Minoo Minoo
• 金额: $ 34.77万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7325665
• 关键词: Attenuated; Cells; Complex; Cyclic AMP-Dependent Protein Kinases; DNA; Development; Gene Expression; Gene Expression Regulation; Genetic Transcription; Goals; Knowledge; Life; Lung; MADH3 gene; Molecular; Nature; Nuclear Protein; Nuclear Proteins; Numbers; Phosphorylation; Protein Biosynthesis; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants; Regulation; Repression; Role; Signal Transduction; Specificity; Testing; Tissues; Transcriptional Regulation; Transforming Growth Factor beta; base; cell type; combinatorial; forkhead protein; homeodomain; in vivo; lung basal segment; lung development; promoter; protein protein interaction; response; surfactant; transcription factor

DESCRIPTION (provided by applicant): The functional linkage between morphogenetic signaling and activation, or repression of gene expression during development is provided by transcription factors. It is now clearly established that none of the transcription factors participating in lung development and regulation of gene expression is exclusively lung-specific. Therefore, specificity must be the function of precise interactions amongst non-specific molecules. Two key transcription factors that are not exclusively lung-specific, but figure importantly in lung gene regulation are NKX2.1 and HNF3. We propose that: Hypothesis: Combinatorial protein-protein interactions between NKX2.1 and HNF3 underlie, at least in part, the molecular basis of lung-specific gene regulation. The following Specific Aims will test the above hypothesis: Specific Aim 1: To characterize physical and functional protein-protein interactions between NKX2.1 and HNF3 in regulation of SpB transcription. Specific Aim 2: To determine the mechanisms by which SMAD3 disrupts NKX2.1-HNF3 interactions. Specific Aim 3: To determine the in vivo functional significance of NKX2.1-HNF3 interactions. The results from the proposed studies will undoubtedly have significant functional implications for combinatorial protein-protein interactions as the molecular basis of tissue and cell-type specificity of gene regulation during lung development.

描述(申请人提供)：形态发生信号和发育过程中基因表达的激活或抑制之间的功能联系是由转录因子提供的。现在已经清楚地证实，参与肺发育和基因表达调控的转录因子都不是肺特有的。因此，特异性必须是非特定分子之间精确相互作用的函数。Nkx2.1和HNF3是两个关键的转录因子，它们不仅是肺特有的，而且在肺基因调控中起着重要的作用。我们认为：假设：Nkx2.1和HNF3之间的组合蛋白-蛋白相互作用至少部分地是肺特异基因调控的分子基础。以下特定目标将验证上述假设：特定目标1：表征Nkx2.1和HNF3之间在调节SPB转录过程中的物理和功能蛋白质-蛋白质相互作用。具体目标2：确定SMAD3干扰Nkx2.1-HNF3相互作用的机制。具体目的3：确定Nkx2.1-HNF3相互作用在体内的功能意义。这些研究的结果无疑将对作为肺发育过程中基因调控的组织和细胞类型特异性的分子基础的蛋白质-蛋白质组合相互作用具有重要的功能意义。