title: A role for BiP as an adjustor for the endoplasmic reticulum stress-sensing protein Ire1.
abstract: In the unfolded protein response, the type I transmembrane protein Ire1 transmits an endoplasmic reticulum (ER) stress signal to the cytoplasm. We previously reported that under nonstressed conditions, the ER chaperone BiP binds and represses Ire1. It is still unclear how this event contributes to the overall regulation of Ire1. The present Ire1 mutation study shows that the luminal domain possesses two subregions that seem indispensable for activity. The BiP-binding site was assigned not to these subregions, but to a region neighboring the transmembrane domain. Phenotypic comparison of several Ire1 mutants carrying deletions in the indispensable subregions suggests these subregions are responsible for multiple events that are prerequisites for activation of the overall Ire1 proteins. Unexpectedly, deletion of the BiP-binding site rendered Ire1 unaltered in ER stress inducibility, but hypersensitive to ethanol and high temperature. We conclude that in the ER stress-sensory system BiP is not the principal determinant of Ire1 activity, but an adjustor for sensitivity to various stresses.
authors.affiliation: Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan. kimata@bs.naist.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kimata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Oikawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishiwata-Kimata
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
mesh_terms: D001665:Binding Sites; D004721:Endoplasmic Reticulum / Q000737:chemistry*; D000431:Ethanol / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013696:Temperature
chemical_list: D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; C060153:KAR2 protein, yeast; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D000431:Ethanol; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases