Overexpression of the gene for polyubiquitin in yeast confers increased secretion of a human leucocyte protease inhibitor.
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.
Chen
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Department of Biochemistry and Molecular Biology, University College London, U.K.
Pioli
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Piper
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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
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