The Roles of the Ubiquitin-Proteasome System in the Endoplasmic Reticulum Stress Pathway

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells, which is essential for synthesis, processing, sorting of protein and lipid metabolism. However, the cells activate a defense mechanism called endoplasmic reticulum stress (ER stress) response and initiate unfolded protein response (UPR) as the unfolded proteins exceed the folding capacity of the ER due to the environmental influences or increased protein synthesis. ER stress can mediate many cellular processes, including autophagy, apoptosis and senescence. The ubiquitin-proteasome system (UPS) is involved in the degradation of more than 80% of proteins in the cells. Today, increasing numbers of studies have shown that the two important components of UPS, E3 ubiquitin ligases and deubiquitinases (DUBs), are tightly related to ER stress. In this review, we summarized the regulation of the E3 ubiquitin ligases and DUBs in ER stress.

Automated summary

The endoplasmic reticulum (ER) is crucial for protein synthesis and metabolism in eukaryotic cells. When unfolded proteins exceed the ER's folding capacity due to environmental influences or increased protein synthesis, cells activate the endoplasmic reticulum stress (ER stress) response. The components of the ubiquitin-proteasome system (UPS), E3 ubiquitin ligases and deubiquitinases (DUBs), are closely related to ER stress.