The Concept of Cellular Proteostasis.

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.


Research in the CRC 969 is divided in three Research Areas.

Research Area A is focused on the analysis of processes that translate the genetic information into active proteins and ensure the localization of the newly translated proteins to the correct cellular compartment which is a prerequisite for establishing and maintaining proteostasis.

Research Area B aims at a better understanding of how posttranslational modifications regulate protein activities in the context of time and space. Protein modifications are essential in proteostasis to increase the plasticity of the proteome and to adjust it to changes of intracellular and extracellular conditions.

Research Area C investigates how the proteome is adapted to diverse stimuli by the specific degradation of proteins or by conformational switches of proteins that may result in protein aggregation.