Figure 1.

The unfolded protein response (UPR).There are three known pathways triggering UPR in ER. (i) PERK (protein kinase RNA-like ER kinase) phosphorylates initiation factor eIF2α, leading to cap independent translation of ATF4 (activating transcription factor 4). ATF4 activates CHOP (C/EBP homologous protein), which can stimulate apoptosis; (ii) IRE1 (inositol-requiring protein 1), is a kinase that leads to activation of RNAse activity. This induces the splicing of XBP1 mRNA and further activates ERAD (ER-associated protein degradation); (iii) following BiP (Immunoglobulin binding protein) dissociation, ATF6 is cleaved by the S1P and S2P proteases into an active form in the Golgi. The activated ATF6 will then cause the activation of ERAD to restore ER (endoplasmic reticulum) homeostasis.