Proteomic characterization of ubiquitin-dependent processes in the secretory pathway

分泌途径中泛素依赖性过程的蛋白质组学表征

• 批准号: 198153153
• 负责人: Professor Dr. Thomas Sommer
• 金额: --
• 依托单位: Forschungsgruppe Intrazelluläre Proteolyse
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/198153153?language=en
• 关键词: Proteomic; characterization; ubiquitin; dependent; processes

This research proposal aims at characterizing non-proteolytic functions of the ubiquitin system that are involved in maintaining homeostasis in the secretory pathway. To this end we plan to purify mem-brane-associated Cdc48 containing protein complexes and identify their functions by genetic and biochemical methods. The AAAATPase Cdc48, in mammals termed p97 or “valosin containing protein” (VCP), is a key player in many ubiquitin-dependent processes like homeotypic membrane fusion, cell cycle control, proteasome-mediated protein degradation and DNA repair. To fulfill these activities, Cdc48/p97 teams up with a large set of diverse ancillary proteins in a temporally and spatially con-trolled manner. Notably, the vast majority of the presently known Cdc48/p97 co-factors contain ubiquitin binding domains or are elsewise linked to the ubiquitin system. However, in most cases we lack in depth knowledge on their molecular function. In the course of this work we plan to isolate novel Cdc48 interacting proteins, determine their function and establish a network of Cdc48 co-factors that integrates this versatile enzyme into particular ubiquitin-dependent processes in the secretory pathway.

该研究计划旨在表征泛素系统的非蛋白水解功能，这些功能涉及维持分泌途径的稳态。为此，我们计划纯化含有膜相关Cdc48的蛋白质复合物，并通过遗传和生化方法鉴定其功能。 AAAATPase Cdc48，在哺乳动物中被称为 p97 或“含缬氨肽蛋白”(VCP)，是许多泛素依赖性过程的关键参与者，如同型膜融合、细胞周期控制、蛋白酶体介导的蛋白质降解和 DNA 修复。为了完成这些活动，Cdc48/p97 以时间和空间受控的方式与大量不同的辅助蛋白合作。值得注意的是，目前已知的绝大多数 Cdc48/p97 辅助因子都含有泛素结合域或以其他方式与泛素系统连接。然而，在大多数情况下，我们缺乏对其分子功能的深入了解。在这项工作过程中，我们计划分离新型 Cdc48 相互作用蛋白，确定其功能并建立 Cdc48 辅助因子网络，将这种多功能酶整合到分泌途径中特定的泛素依赖性过程中。