CORE 2 DB2: PROTEOLYTIC REGULATION OF HIF-1ALPHA

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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 降解因子（HIF）-1 alpha。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，

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