Fig. 2.

Three UPR signaling pathways. Under ER stress, ATF6 is processed to form active p50 ATF6, which is then transported to the nucleus to activate the transcription of genes containing an ERSE [25–27]. IRE1 cleaves 26 nucleotides from XBP1 mRNA to generate spliced XBP1 mRNA, which is translated into the active XBP1(s) protein. Subsequently, XBP1(s) activates the transcription of genes containing an UPRE [28–31]. Similarly, PERK is activated under cellular stress, which phosphorylates eIF2α and reduces protein synthesis to relieve ER stress [32, 33]