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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#_4 http://www.w3.org/ns/prov#value FIG. 7. The signaling arms of the mammalian UPR diverge to regulate some targets and converge to regulate others. The mammalian UPR activates three signal transducers, ATF6, Ire1, and PERK. 1) Activation of ATF6 leads to increased expression of genes regulated by ERSEs in their promoters including ER chaperones like BiP and GRP94, as well as the transcription factor XBP-1. Activation of Ire1 leads to alternative XBP-1 splicing, which in turn up-regulates XBP-1 specific targets like ERdj4, as well as targets with ERSEs in their promoter. A PERK-dependent target other than ATF4 can influence the activation of the ERSE site by an unknown mechanism, which is indicated by a question mark in the schematics. 2) PERK activation leads to eIF-2{alpha} phosphorylation, which allows the expression of the ATF4 transcription factor that in turn induces GADD34 transcription. There is no evidence at this time for members of the ATF6 and Ire1/XBP-1 pathways to impact on the PERK pathway. 3) Finally, the ATF6, Ire1/XBP-1 and PERK pathways converge to optimally induce targets that include CHOP and Herp. Those targets that are downstream of the PERK branch of the UPR are shared with various other cellular stress conditions like heme deficiency, amino acid deprivation, and dsRNA expression. These stresses all activate an eIF-2{alpha} kinase and as a result induce downstream targets like ATF4 and GADD34, as well as those that are dually regulated by both the shared and the ER stress-specific branches of the UPR, which are represented by CHOP and Herp. http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/14742429 http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/14742429 http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#_4 http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0#pubinfo http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0 http://purl.org/dc/terms/created 2014-07-03T14:30:19.919+02:00 http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0 http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RA2ykK8FR3Pv26-YF_MPWiApdzAAyF6SSQs1BkWskN5V0 http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234