CORE 2 DB2: PROTEOLYTIC REGULATION OF HIF-1ALPHA

核心 2 DB2：HIF-1ALPHA 的蛋白水解调节

• 批准号: 7622857
• 负责人: Jeffrey W Smith
• 金额: $ 7.29万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7622857
• 关键词: Automobile Driving; Biological; Calculi; Central Nervous System Neoplasms; Chimeric Proteins; Complex; Computer Analysis; Computer Retrieval of Information on Scientific Projects Database; Defect; Endopeptidases; Eye; Funding; Grant; Hypoxia Inducible Factor; Institution; Japanese Population; Pathway interactions; Patients; Peptide Hydrolases; Regulation of Proteolysis; Research; Research Personnel; Resources; Role; Source; Testing; Tetraodontidae; Torafugu; Ubiquitin-Protein Ligase Complexes; United States National Institutes of Health; VHL protein; Von Hippel-Lindau Syndrome; Work; angiogenesis; link protein; methionine aminopeptidase 2; multicatalytic endopeptidase complex

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Driving Biological Project 2: Proteolytic Regulation of HIF-lalpha: An Ancient Protease Pathway Regulates the Von Hippel-Lindau Angiogenesis Network Patients with von Hippel-Lindau syndrome present with highly vascularized tumors of the CNS and the eye, because of a pro-angiogenic defect in the proteasome pathway. The von Hippel-Lindau protein is part of an E3 ubiquitin-protein ligase complex. This complex targets hypoxia-inducible factor (HIF)-1alpha for degradation. Our computational analysis of the Japanese pufferfish (Fugu rubripes) reveals an ancient fusion protein comprised of the von Hippel-Lindau protein, and two proteases, methionine aminopeptidase-2, and a LON-like protease. We plan to test the Rosetta stone hypothesis, namely that these three proteins are linked in a proteolytic network involved in regulating HIF-lalpha. Our work will include attempts to identify the substrates for each protease, and efforts to test their role in the HIF-lalpha pathway

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 驱动生物学项目2：HIF-1 α的蛋白水解调节：一种古老的蛋白酶 调节Von Hippel-Lindau血管生成网络的途径 von Hippel-Lindau综合征患者表现为CNS和CNS的高度血管化肿瘤， 眼睛，因为蛋白酶体途径中的促血管生成缺陷。希佩尔-林道号 蛋白是E3泛素-蛋白连接酶复合物的一部分。该复合物靶向低氧诱导的 因子（HIF）-1 α降解。我们对日本河豚（Fugu rubripes）的计算分析 揭示了一种由von Hippel-Lindau蛋白和两种蛋白酶组成的古老融合蛋白， 甲硫氨酸氨肽酶-2和LON样蛋白酶。我们计划测试罗塞塔石碑 假设，即这三种蛋白质在蛋白水解网络中连接， 调节HIF-1 α。我们的工作将包括尝试确定每种蛋白酶的底物， 为了测试它们在HIF-1 α通路中的作用，