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Endoplasmic reticulum stress compromises the ubiquitin-proteasome system
Victoria Menéndez-Benito1, Lisette G G C Verhoef, Maria G Masucci
1Department of Cell and Molecular Biology, The Medical Nobel Institute, Karolinska Institutet, PO Box 285, Von Eulers väg 3, S-171 77 Stockholm, Sweden.
Human Molecular Genetics
|August 17, 2005
Summary
Endoplasmic reticulum (ER) stress inhibits the ubiquitin-proteasome system (UPS), leading to protein accumulation in conformational diseases. This study links ER stress to impaired UPS function, explaining disease progression.
Area of Science:
- Cellular Biology
- Molecular Biology
- Pathophysiology
Background:
- Endoplasmic reticulum (ER) stress and impaired ubiquitin-proteasome system (UPS) activity are linked to conformational diseases.
- The interplay between ER stress and UPS function in these diseases remains unclear.
Purpose of the Study:
- To investigate the relationship between ER stress and UPS functionality.
- To determine if ER stress impacts the degradation of UPS substrates.
Main Methods:
- Cells and transgenic mice were subjected to ER stress using various stressors.
- The degradation rates of ER and nuclear/cytosolic UPS reporter substrates were monitored.
- The clearance of UBB+1, an aberrant ubiquitin, was assessed under ER stress conditions.
Main Results:
- ER stressors delayed the degradation of an ER reporter substrate.
- ER stress led to the accumulation of nuclear/cytosolic UPS reporter substrates in cells and mice.
- Impaired clearance of UBB+1 was observed during ER stress, indicating general UPS impairment.
Conclusions:
- ER stress exerts a general inhibitory effect on the ubiquitin-proteasome system.
- Compromised UPS function during ER stress may contribute to misfolded protein accumulation and cellular vulnerability in conformational diseases.