RP1: Identification of ubiquitin-dependent pathways involved in neuron-specific protein degradation

RP1：鉴定参与神经元特异性蛋白质降解的泛素依赖性途径

• 批准号: 45502530
• 负责人: Professor Dr. Thorsten Hoppe
• 金额: --
• 依托单位: Institut für Genetik
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/45502530?language=en
• 关键词: RP1; Identification; ubiquitin; dependent; pathways

The ubiquitin/proteasome system (UPS) is pivotal for the elimination of misfolded or regulatory proteins, and plays a crucial role in correct neuronal development and function. Attachment of several ubiquitin molecules in form of a polyubiquitin chain usually involves three classes of enzymes: a ubiquitin-activating enzyme (El), a ubiquitinconjugating enzyme (E2), and a ubiquitin ligase (E3). In some cases however polyubiquitylation requires the additional activity of ubiquitin chain elongation factors, termed E4 enzymes.The central objective of our proposed research is to identify ubiquitin-dependent pathways involved in neuron-specific protein degradation. Using green fluorescent protein (GFP)-based substrates that allow rapid quantification of ubiquitin-dependent proteolysis, we have established an in vivo degradation assay in different tissues of the model organism Caenorhabditis elegans. The identification of proteolytic pathways specific for neurons and other tissues will provide novel mechanistic insights into the UPS and neuronal differentiation.

泛素/蛋白酶体系统是消除错误折叠或调节蛋白的关键，在正确的神经元发育和功能中起着至关重要的作用。几个泛素分子以多泛素链的形式附着通常涉及三类酶：泛素激活酶（El），泛素结合酶（E2）和泛素连接酶（E3）。然而，在某些情况下，多泛素化需要泛素链延伸因子（称为E4酶）的额外活性。我们提出的研究的中心目标是确定参与神经元特异性蛋白质降解的泛素依赖途径。利用基于绿色荧光蛋白（GFP）的底物，可以快速定量分析泛素依赖的蛋白质水解，我们在模式生物秀丽隐杆线虫的不同组织中建立了体内降解实验。神经元和其他组织特异性蛋白水解途径的鉴定将为UPS和神经元分化提供新的机制见解。