TY - JOUR
T1 - Structural basis of the unfolded protein response
AU - Korennykh, Alexei
AU - Walter, Peter
PY - 2012
Y1 - 2012
N2 - The unfolded protein response (UPR) is a network of intracellular signaling pathways that maintain the protein-folding capacity of the endoplasmic reticulum (ER) in eukaryotic cells. Dedicated molecular sensors embedded in the ER membrane detect incompletely folded or unfolded proteins in the ER lumen and activate a transcriptional program that increases the abundance of the ER according to need. In metazoans the UPR additionally regulates translation and thus relieves unfolded protein load by globally reducing protein synthesis. If homeostasis in the ER cannot be reestablished, the metazoan UPR switches from the prosurvival to the apoptotic mode. The UPR involves a complex, coordinated action of many genes that is controlled by one ER-embedded sensor, Ire1, in yeasts, and three sensors, Ire1, PERK, and ATF6, in higher eukaryotes, including human. We discuss the emerging molecular understanding of the UPR and focus on the structural biology of Ire1 and PERK, the two recently crystallized UPR sensors.
AB - The unfolded protein response (UPR) is a network of intracellular signaling pathways that maintain the protein-folding capacity of the endoplasmic reticulum (ER) in eukaryotic cells. Dedicated molecular sensors embedded in the ER membrane detect incompletely folded or unfolded proteins in the ER lumen and activate a transcriptional program that increases the abundance of the ER according to need. In metazoans the UPR additionally regulates translation and thus relieves unfolded protein load by globally reducing protein synthesis. If homeostasis in the ER cannot be reestablished, the metazoan UPR switches from the prosurvival to the apoptotic mode. The UPR involves a complex, coordinated action of many genes that is controlled by one ER-embedded sensor, Ire1, in yeasts, and three sensors, Ire1, PERK, and ATF6, in higher eukaryotes, including human. We discuss the emerging molecular understanding of the UPR and focus on the structural biology of Ire1 and PERK, the two recently crystallized UPR sensors.
KW - ATF6
KW - Ire1
KW - PERK
KW - RNase
KW - kinase
KW - mechanism
UR - http://www.scopus.com/inward/record.url?scp=84870159094&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870159094&partnerID=8YFLogxK
U2 - 10.1146/annurev-cellbio-101011-155826
DO - 10.1146/annurev-cellbio-101011-155826
M3 - Article
C2 - 23057742
AN - SCOPUS:84870159094
SN - 1081-0706
VL - 28
SP - 251
EP - 277
JO - Annual review of cell and developmental biology
JF - Annual review of cell and developmental biology
ER -