A yeast selection system for the detection of proteasomal activation

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The ubiquitin proteasome system (UPS) is vital for protein homeostasis in eukaryotic cells.
• UPS dysfunction is implicated in diseases involving protein misfolding and aggregation.
• Enhancing UPS activity is a potential therapeutic strategy for these diseases, but its mechanisms are not fully understood.

Purpose of the Study:

• To develop a novel yeast selection platform for genome-wide identification of UPS activators.
• To enable high-throughput screening for compounds that modulate UPS function.

Main Methods:

• Engineered the Saccharomyces cerevisiae URA3 gene to act as a UPS-dependent degradation substrate.
• Fused UPS-sensitive tags to the URA3 protein.
• Linked UPS activity to cell growth in yeast.

Main Results:

• Developed a functional yeast selection platform for identifying UPS activators.
• Demonstrated that the engineered URA3 variant links UPS activity to cell viability.
• Established a tool for genome-wide screening of UPS modulators.

Conclusions:

• The developed yeast platform facilitates high-throughput, genome-wide discovery of UPS activators.
• This platform can identify novel therapeutic targets for protein misfolding diseases.
• Further studies using this platform will advance understanding and treatment of UPS-related disorders.