REGULATION OF VEGF MRNA STABILITY BY HYPOXIA

缺氧对 VEGF mRNA 稳定性的调节

• 批准号: 6370004
• 负责人: HENRY M FURNEAUX
• 金额: $ 3.59万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6370004
• 关键词: angiogenesis; gene expression; genetic regulation; genetic regulatory element; hypoxia; messenger RNA; molecular cloning; protein structure; transcription factor; vascular endothelial growth factors

DESCRIPTION (Adapted from Investigator's Abstract): Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis in diabetic retinopathy, cancer and coronary heart disease. The expression of VEGF is tightly controlled to the cellular oxygen tension. Previous studies have shown that VEGF mRNA is markedly stabilized under hypoxic conditions. The molecular mechanisms underlying the regulation of VEGF mRNA stability are not well understood. In the preliminary results the applicant showed that the stability of VEGF mRNA is controlled by a cis acting element in its 3'UTR. They have also identified a trans acting factor (HuR) that binds to this element and increases the expression of VEGF. In addition, they show that HuR itself is regulated by hypoxia. This proposal will focus on the role of HuR in hypoxic regulation of VEGF mRNA stability. The proposed studies may be important since they could lead to the generation of new drugs that will regulate VEGF expression at the post transcriptional level. The specific aims of the proposal are the following: (1) To determine the fine structure of the HuR/VEGF mRNA complex. To generate mutations in both the mRNA element and HuR and determine their effect on VEGF expression; (2) To design selective inhibitors of HuR/VEGF mRNA complexes; (3) To identify and clone HuR associate proteins that modify its activity; (4) To determine how hypoxia regulates HuR expression; and (5) To determine how HuR stabilizes VEGF mRNA.

描述（改编自研究者摘要）：