The endoplasmic reticulum (ER) is a principal site for folding and maturation of transmembrane, secretory and ER-resident proteins. Perturbations that alter ER homeostasis can lead to accumulation of unfolded proteins (UPs),which is a threat to all living cells. To cope with the stress, cells activate an intracellular signaling pathway – the unfolded protein response(UPR). The UPR is an integrated intracellular signaling pathway that transmits information about the protein folding status in the ER lumen to the cytoplasm and the nucleus. The UPR includes transcriptional induction of UPR genes (red arrows), translational attenuation of global protein synthesis (black arrows)and ER-associated degradation (ERAD) (green arrows). These divergent outputs provide adaptive responses for survival. If the protein-folding defect is not corrected, cells undergo apoptosis (light-blue arrows). The three major transducers of the UPR are PERK, IRE1 and ATF6. FIG1
PERK is an ER transmembrane protein kinase that phosphorylates the αsubunit of translation initiation...
