Figure 1: Schematic showing activation of the three arms of the UPR. The three ER stress sensors PERK, IRE1 and ATF6 are kept in their inactive state through interaction with the ER chaperone GRP78 (BiP). In response to accumulating misfolded/unfolded proteins in the ER, GRP78 dissociates from the lumilal domain of these sensors, leading to their activation. The concerted action of PERK, IRE1 and ATF6 activates a transcriptional response which can be adaptive or apoptotic and is essential for cell survival during ER stress. The same transcriptional response also contributes to tumour development and progression.