title: Absence of typical unfolded protein response in primary cultured cystic fibrosis airway epithelial cells.
abstract: We examined whether the unfolded protein response is activated in cells expressing incorrectly folded cystic fibrosis transmembrane conductance regulator. Airway epithelial cells from three control and three CF patients homozygous for the deltaF508 mutation were tested. There were no differences in protein expression of the pro-apoptotic factor C/EBP homologous protein (CHOP) or the endoplasmic reticulum (ER) chaperone binding Ig protein. Nor were there differences in phosphorylation of protein kinase R-like ER kinase or eukaryotic initiation factor-2alpha, or the splicing of X-box binding protein (XBP)-1. However, CF cells showed increased mRNA expression of CHOP and XBP-1. A proteasome inhibitor increased CHOP expression in CF cells, suggesting that enhanced proteasome activation is responsible for the observed post-transcriptional regulation. Finally, CF cells were resistant to apoptosis, suggesting that post-transcriptional regulation of CHOP prevents apoptosis. While CHOP and XBP-1 mRNA expression is increased in CF cells, the classic UPR is not present.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109-0688, USA.
authors.forename: Suparna
authors.initials: S
authors.lastname: Nanua
authors.forename: Umadevi
authors.initials: U
authors.lastname: Sajjan
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D017209:Apoptosis; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D017510:Protein Folding; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D019892:eIF-2 Kinase; C497111:ATF6 protein, human; C497249:DDIT3 protein, human; C101003:ELF2 protein, human