Fig. 1
From: Endoplasmic reticulum stress targeted therapy for breast cancer
Overview of the three sensors of UPR. Under normal conditions, the three proteins (IRE1a, PERK, and ATF6) bind to the molecular chaperone protein GRP78. While under stress conditions, GRP78 releases from the three sensors, resulting in their activation. Each activation pathway has a different signal transduction mechanism. IRE1α splices XBP1 mRNA to encode for the transcription factor XBP1s, which promotes the expression of genes involved in the protein folding and erase induce and add in ERAD. PERK undergoes oligomerization and auto-phosphorylation which then promotes the phosphorylation of phosphorylate eIF2a, leading to general translational attenuation while selectively activating ATF4. ATF6 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes S1P and S2P protease cleavage, which releases the active form of ATF6