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Updated: Sep 3, 2025
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Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
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USP5 enhances SGTA mediated protein quality control.
Jake Hill1,2, Yvonne Nyathi1,2
1School of Life Sciences, Joseph Banks Laboratories, University of Lincoln, Lincoln, United Kingdom.
Plos One
|July 27, 2022
Summary
The study identifies ubiquitin specific peptidase 5 (USP5) as a deubiquitinating enzyme that collaborates with SGTA to regulate mislocalised membrane proteins (MLPs). This interaction impacts MLP degradation, influencing aggregate formation in diseases.
Area of Science:
- Cellular Biology
- Protein Quality Control
- Neurodegenerative Disease Research
Background:
- Mislocalised membrane proteins (MLPs) aggregate due to exposed hydrophobic regions, posing cellular risks.
- SGTA is known to regulate MLP quality control, promoting deubiquitination and accumulation in cytosolic inclusions.
Purpose of the Study:
- Identify deubiquitinating enzymes (DUBs) interacting with SGTA in MLP quality control.
- Investigate the role of USP5 in regulating MLP fate and aggregation.
Main Methods:
- Co-immunoprecipitation assays to detect protein complexes.
- Western blotting to assess protein levels.
- Gene knockdown and overexpression studies.
Main Results:
- Ubiquitin specific peptidase 5 (USP5) identified as a DUB interacting with SGTA.
- USP5 and SGTA form a complex, enhanced by MLPs.
- USP5 is crucial for SGTA-mediated accumulation of MLPs; its absence compromises this effect.
- USP5 modulates MLP steady-state levels, impacting proteasomal degradation.
Conclusions:
- The SGTA-USP5 interaction regulates MLP quality control by enabling escape from proteasomal degradation.
- This mechanism influences aggregate formation relevant to neurodegenerative diseases and type II diabetes.
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