Regulation of proteasome homeostasis in yeast

• Applicant: Professor Dr. Dieter H. Wolf, since 10/2010
• Subject Area: Cell Biology
• Term: from 2009 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 150337473

Biological processes are allowed to be slightly unreliable as long as quality control exists. Failed protein quality control mechanisms result in the aggregation of misfolded and defective proteins, typical of many neurodegenerative disorders. The key enzyme of selective degradation of these proteins is the proteasome. Proteasomes are composed of proteolytically active core and regulatory complexes which comprise ~ 33 different subunits. In this project, we want to investigate quality control mechanisms of the proteasome itself. Normally, proteasomededicated chaperones are degraded upon the completion of proteasome maturation. However, how do cells deal with incompletely matured or pre-activated proteasomes ? In yeast, we recently found that the conserved HEAT-like repeat protein Blm10 distinguishes proteasome conformations and sequesters pre-activated proteasomes. Ecm29, a protein structurally related to Blm10, also emerged as a possible player in editing proteasome configurations. We will investigate whether alternatively / aberrantly configured proteasome assemblies are advantageous under certain physiological conditions, whether they are remodelled, stored or degraded. The pathways responsible for checking the correctness and for maintaining the functionality of proteasomes will be challenged under stress conditions.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Professorin Dr. Cordula Enenkel, from 8/2009 until 10/2010