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Glucose on the sugar side chains of proteins keeps unfolded proteins in the ER. Mannoses on sugar side chains act as a timer for protein folding. Unfolded proteins in the ER are threaded through a retrotranslocon into the cytosol where they are ubiquitylated and digested. IRE1, ATF6 and PERK sense the amount of unfolded protein and generates several responses to reduce the effects and amount of unfolded protein.
The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER).It is a stress response that has been found to be conserved between all mammalian species, as well as yeast and worm organisms.This article focuses on the mammalian response. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum.ranslation Attenuation and Cell Cycle Arrest by the PERK Receptor This occurs within minutes to hours of UPR activation to prevent further translational loading of the ER. PERK (protein kinase RNA-like endoplasmic reticulum kinase) activates itself by oligomerization and autophosphorylation of the free luminal domain.