Stress-sensing mechanisms in the unfolded protein response: similarities and differences between yeast and mammals

The unfolded protein response is an adaptive stress response that responds to the imbalance between the entry of newly synthesized unfolded proteins and the inherent folding capacity in the endoplasmic reticulum (ER). Various environmental stresses and changes in physiological conditions can result in the accumulation of unfolded proteins in the ER, which is sensed through ER transmembrane protein sensors named inositol requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK) and activating transcription factor 6 (ATF6), and the sensed signals are transduced to the cytosol and the nucleus. IRE1 is a prototype ER stress sensor that is evolutionarily conserved from yeast to humans. Higher eukaryotes have evolved two other sensors, PERK and ATF6. This review focuses on the current progress in our understanding of stress-sensing mechanisms, in particular, the similarities and differences between yeast and mammals.