Figure 7.

The three arms of the unfolded protein response stress-responsive signaling pathway. Proteostasis network capacity in the endoplasmic reticulum (ER) is matched to the level of newly synthesized proteins passing through the secretory pathway by the activation of intracellular signaling pathways collectively referred to as the unfolded protein response. The unfolded protein response responds to the accumulation of misfolded proteins within the lumen of the endoplasmic reticulum. Accumulation of unfolded proteins activates signaling pathways in the cytosol via the trans-membrane stress sensor proteins IRE1, ATF6, and PERK. Activation of the unfolded protein response results in translational attenuation of protein synthesis and transcriptional activation of genes regulated by the transcription factors XBP1s, ATF4, and ATF6 resulting from the three signaling arms of the unfolded protein response. (Figure adapted from Wiseman et al. [2010] and reprinted, with permission, from Elsevier © 2010.)