WT1 P53 INTERACTIONS IN IGF I RECEPTOR REGULATION

WT1 P53 在 IGF I 受体调节中的相互作用

• 批准号: 2736212
• 负责人: Charles T Roberts
• 金额: $ 2万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2736212
• 关键词: gene expression; genetic promoter element; growth factor receptors; insulinlike growth factor; receptor binding; receptor expression; tissue /cell culture; transcription factor; tumor suppressor proteins

DESCRIPTION The IGF-I-R mediates the biological actions of the IGFs, and has been implicated in malignant transformation. The long-term objectives of this proposal are (1) to determine how p53 (a widely distributed nuclear protein which functions as a tumor suppressor by blocking progression of cells through the cell cycle by binding to components of basal transcription machinery) and WT1 (an organ-specific transcription factor which represses IGF-I-R expression by binding to specific sites in the IGF-I-R promoter) cooperate to repress IGF-I-R gene expression, and (2) to determine how mutations of either WT1 or p53 may disrupt the interactions between both proteins and/or between these proteins and the IGF-I-R promoter, resulting in deregulated expression of the receptor. Pilot studies suggest that p53 repression of IGF-I-R results from binding of p53 to TBP, presumably precluding the formation of a functional transcription initiation complex. The specific aims of the proposal are to demonstrate functional interaction between WT1 and p53, to analyze the WT1/p53 interaction on the IGF-I-R promoter in vitro, and to verify this interaction in the regulation of endogenous IGF-I-R.

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