Unfolded Protein Response Pathway (UPR)

The unfolded protein response (UPR) is a highly conserved cellular stress response pathway that is activated by the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER). Its primary function is to maintain ER protein homeostasis and protect cells from proteotoxic stress. The UPR achieves this by: halting general protein translation to reduce the influx of new proteins into the ER, increasing production of molecular chaperones and folding enzymes to enhance folding capacity, promoting degradation of misfolded proteins through ER-associated degradation pathways. If these adaptive responses fail to restore normal conditions, prolonged UPR activation can trigger apoptosis, leading to cell death. The UPR plays essential roles in: maintaining cellular health under physiological and pathological conditions, regulating immune cell development, differentiation, function, and survival, influencing various physiological processes in tissues with high secretory demand (e.g., pancreas, liver), determining cell fate decisions between adaptation/survival versus programmed cell death during chronic or severe stress. Dysregulation or sustained activation of the UPR has been implicated in numerous diseases including: neurodegenerative disorders, prion diseases, diabetes mellitus, cancer.

Other names

ER Stress ResponseUPR pathway