During cellular stress the protein folding capacity of the ER is diminished. In order to maintain homeostasis and ensure proper protein folding cells activate the unfolded protein response (UPR), a signaling network consisting of sensors and effectors to enhance the chaperone activity of the cell, increase degradation of accumulated proteins, and/or trigger apoptosis. Inositol-requiring enzyme 1 (IRE1), an ER-transmembrane protein, is an essential component of the UPR pathway important for sensing and responding to ER stress.
During times of cellular stress overloading of the protein folding machinery leads to the accumulation of incorrectly folded proteins. This triggers the unfolded protein response (UPR) in order to try to reestablish homeostasis or, if this fails, to induce apoptosis. The UPR pathway is mediated by a group of ER-associated transmembrane receptors including activating transcription factor 6 (ATF6). The presence of misfolded proteins is monitored by BiP, an Hsp70 family member.
