PathwayStep4049 PathwayStep4037 PERK regulated gene expression Activation of Chaperones by ATF6-alpha Unfolded Protein Response Authored: May, B, 2009-06-02 00:51:49 Edited: May, B, Gopinathrao, G, 2008-11-19 19:22:37 GENE ONTOLOGYGO:0030968 Pubmed15952902 Pubmed16365312 Pubmed18038217 Pubmed18048764 Pubmed18436705 Reactome Database ID Release 43381119 Reactome, http://www.reactome.org ReactomeREACT_18356 Reviewed: D'Eustachio, P, Matthews, L, Gillespie, ME, 2008-12-02 16:25:31 Reviewed: Urano, F, 2010-04-30 The Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER during times of unusually high secretion activity. Analysis of mutants with altered UPR, however, shows that the UPR is also required for normal development and function of secretory cells.<br>One level at which the URP operates is transcriptional and translational regulation: mobilization of ATF6 and IRE1 leads to increased transcription of genes encoding chaperones, and mobilization of PERK (pancreatic eIF2alpha kinase) leads to phosphorylation of the translation initiation factor eIF2alpha and global down-regulation of protein synthesis. These three regulatory pathways are annotated here. Activation of Chaperones by IRE1alpha PathwayStep3984