CORE 2 DB2: PROTEOLYTIC REGULATION OF HIF-1ALPHA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 驱动生物计划2：HIF-α的蛋白分解调节：一种古老的蛋白水解酶 Von Hippel-Lindau血管生成网络的调控途径 Von Hippel-Lindau综合征患者表现为高度血管化的中枢神经系统肿瘤和 眼睛，因为蛋白酶体途径中的促血管生成缺陷。冯·希佩尔-林道 蛋白质是E3泛素-蛋白质连接酶复合体的一部分。这种复合体针对低氧诱导的 因子(HIF)-1α，用于降解。我们对日本河豚(河豚)的计算分析 揭示了一种古老的融合蛋白，由冯·希佩尔-林道蛋白和两种蛋白酶组成， 蛋氨酸氨基肽酶-2和一种类似LON的蛋白酶。我们计划测试罗塞塔石碑 假说，即这三种蛋白质连接在一个蛋白分解网络中，参与了 调节HIF-α。我们的工作将包括尝试确定每种蛋白酶的底物，以及 努力测试它们在HIF-α途径中的作用

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