The mammalian unfolded protein response pathway

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The mammalian unfolded protein response pathway The mammalian unfolded protein response pathway. Accumulation of misfolded proteins in the ER lumen catalyzes the dissociation of GRP78 from ATF6, PERK, and IRE1. ATF6 is activated by the S1P and S2P proteases and transported to the nucleus; it activates transcription by binding to the ERSE element in the promoter region of the response genes. IRE1 forms oligomers, and after activation it cleaves Xbp1 mRNA, resulting in formation of a potent Xbp1 transcription factor, which is capable of binding ERSE elements and activating transcription. PERK is activated in an IRE1-like manner and stalls protein synthesis by phosphorylation of eIF2α. ATF6, activating transcription factor 6; ER, endoplasmic reticulum; ERSE, endoplasmic reticulum stress response element; GRP78, glucose regulated protein 78; IRE1, inositol-requiring 1; PERK, protein kinase-like ER kinase; S1P, site-1 protease; S2P, site-2 protease; Xbp1, X-box binding protein 1. Source: Protein Folding and Misfolding: The Role of Cellular Protein Quality Control Systems in Inherited Disorders, The Online Metabolic and Molecular Bases of Inherited Disease Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: https://ommbid.mhmedical.com/DownloadImage.aspx?image=/data/books/971/ch13_1fg14.png&sec=62640639&BookID=971&ChapterSecID=62640472&imagename= Accessed: March 04, 2018 Copyright © 2018 McGraw-Hill Education. All rights reserved