ER-associated protein degradation (ERAD): The machinery for recognition, retro-translocation and degradation of misfolded proteins of the ER

• Applicant: Dr. Alexandra Stolz, since 1/2019
• Subject Area: Biochemistry ; Cell Biology
• Term: from 2010 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 165917224

Correct folding of all proteins is essential for every cell. Misfolding does not only lead to loss of protein function but can also lead to the formation of protein aggregates. Also a mistaken attachment to functional proteins is possible by this inducing malfunction of the formerly functional protein. Misfolding of proteins is not only an accidental process which occurs continuously but is especially prominent upon application of stresses as heat, oxygen radicals or heavy metal ions. Also mutations constitute a prominent cause of protein misfolding. Therefore the cell possesses highly effective mechanisms of protein quality control. These mechanisms guarantee the recognition of misfolded proteins and their efficient elimination. Defects in protein quality control lead to cellular defects and constitute the cause of a multitude of severe diseases in man as are neurodegenerative diseases ( Alzheimer-, Parkinson-, Creutzfeldt Jakob disease), diabetes or cancer. All major cell compartments of a eukaryotic cell possess protein quality control and elimination mechanisms. It is the aim of this proposal to elucidate the components and mechanisms which recognize and eliminate the misfolded proteins of the endoplasmic reticulum, the central organelle of the secretory system. These studies will be done using the yeast Saccharomyces cerevisiae which has turned out to be an excellent model organism for elucidating the basic "housekeeping functions" of the eukaryotic cell. In the past, studies on this organism have resulted in groundbreaking results in the field and made yeast a pacemaker in the field of ER associated protein degradation.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Dieter H. Wolf, until 12/2018