Figure 1.

Transmembrane regulators of the unfolded protein response (UPR). During activation of the UPR, ATF6 translocates to the Golgi and is cleaved, before it activates a series of downstream targets, such as endoplasmic reticulum‐associated degradation (ERAD), CHOP, BiP and XBP1. PERK autophosphorylates, and in turn phosphorylates eIF2α and Nrf2, which targets downstream UPR targets. IRE1α is also activated by autophosphorylation, which phosphorylates JNK, while also activating XBP1. IRE1α removes the 26 base pair intron from unspliced XBP1 mRNA resulting in expression of the active isoform from the spliced mRNA.