What are the Key Pathways Involved in ER Stress and Cancer?
Three primary signaling pathways mediate the UPR: PERK (Protein kinase RNA-like Endoplasmic Reticulum Kinase), IRE1 (Inositol-Requiring Enzyme 1), and ATF6 (Activating Transcription Factor 6). Each of these pathways has distinct roles in managing ER stress:
PERK Pathway: PERK phosphorylates eIF2α, leading to a temporary reduction in protein translation and allowing the cell to manage the protein load. IRE1 Pathway: IRE1 splices XBP1 mRNA to produce a potent transcription factor that upregulates genes involved in protein folding and ER-associated degradation (ERAD). ATF6 Pathway: ATF6 translocates to the Golgi apparatus upon ER stress, where it is cleaved to release a cytoplasmic fragment that functions as a transcription factor, promoting the expression of UPR target genes.
