Figure 2

The two branches of the unfolded protein response. As a result of accumulation of misfolded proteins in the ER, the unfolded protein response is initiated. Three signal transduction pathways coordinate the pathway and require the dissociation of the ER chaperone BiP. The kinases are: PKR-like kinase (PERK). PERK activation sends both pro-and anti-apoptotic signals but its main function is translation attenuation via phosphorylation of eIF2α which reduces the ER load. ATF6 induces expression of chaperones like BiP, but also the apoptosis factor CHOP. IRE1 is activated and becomes an endonuclease that process the XBP1 mRNA. XBP1 protein is a transcription factor that drives the transcription of both pro- and anti-apoptotic genes. The delicate balance between the protective and destructive branches of the UPR determines if the cell will overcome the stress or will die via the PCD pathway.