Stimulus- and time-dependent protein dynamics of the autophagosome analyzed by quantitative mass spectrometry

通过定量质谱分析自噬体的刺激和时间依赖性蛋白质动力学

• 批准号: 180712627
• 负责人: Professor Dr. Jörn Dengjel
• 金额: --
• 依托单位: Départment de Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/180712627?language=en
• 关键词: Stimulus; time; dependent; protein; dynamics

We are investigating time- and stimulus-specific differences of the autophagosomal protein composition by quantitative mass spectrometry-based proteomics. Our work will yield new insights into a basic cellular degradation pathway whose deregulation is involved in numerous diseases, inter alia in cancer development and bacterial and viral immune evasion. Thus, we expect that the described molecular networks will allow the design of new therapeutic strategies in diverse disease settings. The autophagosomal/lysosomal system is next to the ubiquitin/proteasome system responsible for the majority of cellular proteolysis. The autophagosome encloses cytosol and organelles targeting them for degradation by lysosomal fusion yielding free amino acids. Autophagy has been regarded as an unspecific bulk degradation pathway. However, lately more and more specific autophagy subtypes are being described and it is still largely unknown which bio-molecules are present under which conditions and to which time point in the autophagosome. We will address these questions by inducing autophagy by different stimuli and analyzing autophagosomes at different time points. In addition, we are investigating the influence of viral infections on autophagosomal composition and the influence of autophagy in viral immune evasion.

我们正在研究的时间和刺激特异性差异的自噬体蛋白质组成的定量质谱为基础的蛋白质组学。我们的工作将产生新的见解基本的细胞降解途径，其失调涉及许多疾病，阿利亚是在癌症的发展和细菌和病毒的免疫逃避。因此，我们期望所描述的分子网络将允许在不同疾病环境中设计新的治疗策略。自噬体/溶酶体系统与负责大部分细胞蛋白水解的泛素/蛋白酶体系统相邻。自噬体包围胞质溶胶和靶向它们的细胞器，用于通过溶酶体融合降解，产生游离氨基酸。自噬被认为是一种非特异性的整体降解途径。然而，最近越来越多的自噬亚型被描述，并且在很大程度上仍然不知道哪些生物分子在哪些条件下以及在自噬体中的哪个时间点存在。我们将通过不同刺激诱导自噬和分析不同时间点的自噬体来解决这些问题。此外，我们正在研究病毒感染对自噬体组成的影响以及自噬在病毒免疫逃避中的影响。