The UPR involves three main signaling pathways: PERK (PKR-like ER kinase), IRE1 (inositol-requiring enzyme 1), and ATF6 (activating transcription factor 6). Each of these pathways helps reduce the load of misfolded proteins and restore ER function. PERK reduces protein synthesis, IRE1 splices XBP1 mRNA to produce a transcription factor that enhances the expression of UPR target genes, and ATF6 moves to the Golgi where it is cleaved to release a transcription factor that upregulates UPR genes.
