title: Overexpression of the gene for polyubiquitin in yeast confers increased secretion of a human leucocyte protease inhibitor.
abstract: We have found an influence of cellular ubiquitin levels over the secretion of human leucocyte elastase inhibitor (elafin) by Saccharomyces cerevisiae. Inactivation of the UBI4 polyubiquitin gene reduced elafin secretion 3 to 4-fold. Conversely ubiquitin overexpression, by galactose induction of an integrated UBI4 gene under GAL1 promoter control, enhanced elafin secretion 7-fold compared to cells wild-type for ubiquitin genes. This influence of ubiquitin levels is exerted at a post-transcriptional step in elafin gene expression, and may represent a chaperone-like action. Ubiquitin overexpression did not affect production of alpha-factor and of certain natural yeast extracellular enzymes even though appreciable free ubiquitin became associated with the yeast periplasm.
authors.affiliation: Department of Biochemistry and Molecular Biology, University College London, U.K.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Pioli
authors.forename: P W
authors.initials: PW
authors.lastname: Piper
mesh_terms: D000595:Amino Acid Sequence; D001704:Biopolymers / Q000235:genetics* / Q000502:physiology; D005690:Galactose / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D019272:Leukocyte Elastase; D007962:Leukocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D025821:Polyubiquitin; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000737:chemistry; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics* / Q000502:physiology
chemical_list: D001704:Biopolymers; D011498:Protein Precursors; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D014452:Ubiquitins; D025821:Polyubiquitin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D005690:Galactose