CORE 2 DB2: PROTEOLYTIC REGULATION OF HIF-1ALPHA

核心 2 DB2：HIF-1ALPHA 的蛋白水解调节

• 批准号: 7725959
• 负责人: Jeffrey W Smith
• 金额: $ 7.6万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725959
• 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

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 驾驶生物学项目2：HIF-Lalpha的蛋白水解调节：一种古老的蛋白酶 途径调节von Hippel-Lindau血管生成网络 von Hippel-Lindau综合征患者患有高度血管化的中枢神经系统和 眼，由于蛋白酶体途径中的促血管生成缺陷。 von Hippel-Lindau 蛋白质是E3泛素蛋白 - 蛋白连接酶复合物的一部分。该复合物靶向缺氧诱导 因子（HIF）-1alpha用于降解。我们对日本河豚（Fugu Rubripes）的计算分析 揭示了一种古老的融合蛋白，该蛋白质由von Hippel-Lindau蛋白和两个蛋白酶组成 蛋氨酸氨基肽酶-2和lon样蛋白酶。我们计划测试Rosetta石头 假设，即，这三种蛋白质在涉及的蛋白水解网络中连接 调节hif-lalpha。我们的工作将包括试图识别每种蛋白酶的底物，以及 努力测试他们在HIF-Lalpha途径中的作用