The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress. Running title: The ISR facilitates activation of ATF6

The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress. Running title: The ISR facilitates activation of ATF6 Brian F. Teske, Sheree A. Wek, Piyawan Bunpo, Judy K. Cundiff, Jeanette N. McClintick, Tracy G. Anthony, and Ronald C. Wek Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202; USA Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, IN 47712; USA *Address correspondence to: Ronald C. Wek, Department of Biochemistry and Molecular Biology, 635 Barnhill Drive, Indiana University School of Medicine, Indianapolis, Indiana 46202; USA. Phone (317) 274-0549; FAX (317) 274-4686; E-mail [email protected]. Tracy G. Anthony, Department of Biochemistry and Molecular Biology, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine – Evansville Health Professions Room 3069, 8600 University Boulevard, Evansville, Indiana 47712; USA. Phone (317) 274-0549; FAX (317) 274-4686; E-mail [email protected]. ABSTRACT Disruptions of the endoplasmic reticulum (ER) that perturb protein folding cause ER stress and elicit an unfolded protein response (UPR) that involves translational and transcriptional changes in gene expression aimed at expanding the ER processing capacity and alleviating cellular injury. Three ER stress sensors PERK, ATF6, and IRE1 implement the UPR. PERK phosphorylation of the α subunit of eIF2 during ER stress