SFB 969: Chemical and Biological Principles of Cellular Proteostasis

SFB 969：细胞蛋白质稳态的化学和生物学原理

• 批准号: 189682160
• 金额: --
• 依托单位: Universität Konstanz
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/189682160?language=en
• 关键词: SFB; 969; Chemical; Biological; Principles

Proteostasis comprises multiple highly conserved and interconnected cellular processes that control the activity of individual proteins in space and time to ensure the functionality of the proteome, its continuous renewal, and its adaptation to environmental changes. At the posttranscriptional level, three main aspects of proteostasis can be defined: Protein biogenesis including translation, folding, transport, and assembly processes; Modulation of protein function, concentration, and localization by posttranslational modification; Protein quality control to recycle or remove misfolded or aggregated proteins to avoid accumulation of toxic products inside the cell. It is known that proteostasis naturally declines during aging or can reach its limits by extreme challenges. The profound consequence of a decline of cellular proteostasis for the entire organism is highlighted by the fact that many human diseases including cancer and neurodegenerative disorders are caused by misregulation of protein activities.To dissect the principles underlying proteostasis, the Collaborative Research Center (CRC) 969 combines, in a highly interdisciplinary and synergistic research approach, the expertise of Chemistry and Biology in order to:(i) understand the regulation of individual protein activities that act at cellular hubs of proteostasis, e.g. in protein folding and assembly, posttranslational modification, and protein degradation. (ii) study processes and mechanisms required to adapt the proteome to specific demands such as metabolic changes, cell division, viral infection, and stress.(iii) develop novel chemical tools and biophysical strategies to simulate, monitor or manipulate protein activities and thereby proteostasis in vitro and in vivo. Research in the CRC 969 carried out in 19 projects centers around three research areas reflecting the life cycle of proteins and thus the key pathways of proteostasis: (A) Protein Biogenesis, (B) Protein Modification, and (C) Protein Aggregation and Degradation.

蛋白质平衡包括多种高度保守和相互关联的细胞过程，这些过程控制单个蛋白质在空间和时间上的活性，以确保蛋白质组的功能、其持续更新和对环境变化的适应。在转录后水平上，蛋白质调控的三个主要方面可以被定义：蛋白质的生物发生，包括翻译、折叠、运输和组装过程；通过翻译后修饰调节蛋白质的功能、浓度和定位；蛋白质质量控制，回收或去除错误折叠或聚集的蛋白质，以避免有毒产物在细胞内积累。众所周知，蛋白质平衡在衰老过程中会自然下降，或者可以在极端挑战下达到极限。包括癌症和神经退行性疾病在内的许多人类疾病都是由蛋白质活性的错误调节引起的，这一事实突显了细胞蛋白质稳定性下降的深刻后果。为了剖析蛋白质稳定性的基本原理，协作研究中心(CRC)969以高度跨学科和协同的研究方法，结合化学和生物学的专业知识，以：(I)了解作用于蛋白质稳定性细胞中心的单个蛋白质活动的调节，例如在蛋白质折叠和组装、翻译后修饰和蛋白质降解。(Ii)研究使蛋白质组适应特定要求所需的过程和机制，如代谢变化、细胞分裂、病毒感染和应激。(Iii)开发新的化学工具和生物物理策略来模拟、监测或操纵蛋白质活性，从而在体外和体内保持蛋白质稳定。在19个项目中开展的CRC969研究集中在反映蛋白质生命周期的三个研究领域，从而反映了蛋白质稳定的关键途径：(A)蛋白质生物发生，(B)蛋白质修饰，(C)蛋白质聚集和降解。