Yeast flavin-containing monooxygenase is induced by the unfolded protein response.
Flavin-containing monooxygenase from yeast (yFMO) carries out the O(2)- and NADPH-dependent oxidation of biological thiols, including oxidizing glutathione to glutathione disulfide. FMO provides a large fraction of the oxidizing necessary for proper folding of disulfide bond-containing proteins; deletion of the enzyme reduces proper folding of endogenous carboxypeptidase Y by about 40%. The enzyme is not essential to cell viability because other enzymes can generate a significant fraction of the oxidizing equivalents required by the cell. However, yFMO is vital to the yeast response to reductive stress. FMO1 deletion mutants grow poorly under reductive stress, and carboxypeptidase Y activity is less than 10% of that in a stressed wild type. The FMO1 gene appears to be under control of an unfolded protein response element and is inducible by factors, such as reductive stress, that elicit the unfolded protein response. Reductive stress can increase yFMO activity at least 6-fold. This increased activity allows the cell to process endogenous disulfide bond-containing proteins and also to allow correct folding of disulfide-bonded proteins expressed from multicopy plasmids. The unfolded protein response is mediated by the Hac1p transcription factor that mediates virtually all of the induction of yFMO triggered by exogenous reducing agents.
Suh
J K
JK
Institute of Cellular Biology, Department of Chemistry, University of Texas, Austin, TX 78712, USA.
Robertus
J D
JD
D050976:Basic-Leucine Zipper Transcription Factors; D002268:Carboxypeptidases / Q000378:metabolism; D043402:Cathepsin A; D002688:Chitinases / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D004790:Enzyme Induction; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D018384:Oxidative Stress; D010105:Oxygenases / Q000096:biosynthesis* / Q000235:genetics; D010957:Plasmids; D017510:Protein Folding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors
D050976:Basic-Leucine Zipper Transcription Factors; D004220:Disulfides; D005656:Fungal Proteins; C091341:HAC1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D002688:Chitinases; D002268:Carboxypeptidases; D043402:Cathepsin A