title: Jagn1 Is Induced in Response to ER Stress and Regulates Proinsulin Biosynthesis.
abstract: The Jagn1 protein was indentified in a SILAC proteomic screen of proteins that are increased in insulinoma cells expressing a folding-deficient proinsulin. Jagn1 mRNA was detected in primary rodent islets and in insulinoma cell lines and the levels were increased in response to ER stress. The function of Jagn1 was assessed in insulinoma cells by both knock-down and overexpression approaches. Knock-down of Jagn1 caused an increase in glucose-stimulated insulin secretion resulting from an increase in proinsulin biosynthesis. In contrast, overexpression of Jagn1 in insulinoma cells resulted in reduced cellular proinsulin and insulin levels. Our results identify a novel role for Jagn1 in regulating proinsulin biosynthesis in pancreatic β-cells. Under ER stress conditions Jagn1 is induced which might contribute to reducing proinsulin biosynthesis, in part by helping to relieve the protein folding load in the ER in an effort to restore ER homeostasis.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Canada.
authors.forename: Courtney
authors.initials: C
authors.lastname: Nosak
authors.affiliation: Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
authors.forename: Pamuditha N
authors.initials: PN
authors.lastname: Silva
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Pietro
authors.initials: P
authors.lastname: Sollazzo
authors.affiliation: Department of Biochemistry & Molecular Biology and Centre for High-Throughput Biology, University of British Columbia, Vancouver, Canada.
authors.forename: Kyung-Mee
authors.initials: KM
authors.lastname: Moon
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Odisho
authors.affiliation: Department of Biochemistry & Molecular Biology and Centre for High-Throughput Biology, University of British Columbia, Vancouver, Canada.
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Canada.|Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Rocheleau
authors.affiliation: Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.
authors.forename: Allen
authors.initials: A
authors.lastname: Volchuk
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D011384:Proinsulin / Q000096:biosynthesis*; D040901:Proteomics; D051381:Rats
chemical_list: D007328:Insulin; D008565:Membrane Proteins; D050505:Mutant Proteins; D011384:Proinsulin