Sterol Esterification in Yeast: A Two-Gene Process

Unesterified sterol modulates the function of eukaryotic membranes. In human cells, sterol is esterified to a storage form by acyl-coenzyme A (CoA): cholesterol acyl transferase (ACAT). Here, two genes are identified, ARE1 and ARE2, that encode ACAT-related enzymes in yeast. The yeast enzymes are 49...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) Vol. 272; no. 5266; pp. 1353 - 1356
Main Authors:	Yang, Hongyuan, Bard, Martin, Bruner, Debora A., Gleeson, Anne, Deckelbaum, Richard J., Aljinovic, Gordana, Pohl, Thomas M., Rothstein, Rodney, Sturley, Stephen L.
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society for the Advancement of Science 31-05-1996 American Association for the Advancement of Science The American Association for the Advancement of Science
Subjects:	Acetates - metabolism Acyltransferases - chemistry Acyltransferases - genetics Acyltransferases - metabolism Amino Acid Sequence Base Sequence Biological and medical sciences Biosynthesis Cell Membrane - metabolism Cell membranes Cells Cells (Biology) Cholesterol Esters - metabolism Classical genetics, quantitative genetics, hybrids Coding Cyclin-Dependent Kinase 8 Cyclin-Dependent Kinases Diploidy DNA DNA, Complementary - genetics Enzymes Ergosterol - metabolism Esterification Esters Eukaryotes Eukaryotic cells Fundamental and applied biological sciences. Psychology Genes Genes, Fungal Genetics of eukaryotes. Biological and molecular evolution Homeostasis Humans Lipids Membranes Molecular Sequence Data Mutation Oleic Acid Oleic Acids - metabolism Open reading frames Redundancy Saccharomyces cerevisiae Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins Sterol O-Acyltransferase - genetics Sterol O-Acyltransferase - metabolism Sterols Sterols - metabolism Thallophyta, bryophyta Transformation, Genetic Vegetals Yeast Yeasts Acyltransferases Yeast Nucleotide sequence Enzyme Transferases Homology Metabolism Esterification Fungi Gene DNA Deletion Genetics Ascomycetes Mutation Saccharomyces cerevisiae Thallophyta Sterol O-acyltransferase Sterol
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Summary:	Unesterified sterol modulates the function of eukaryotic membranes. In human cells, sterol is esterified to a storage form by acyl-coenzyme A (CoA): cholesterol acyl transferase (ACAT). Here, two genes are identified, ARE1 and ARE2, that encode ACAT-related enzymes in yeast. The yeast enzymes are 49 percent identical to each other and exhibit 23 percent identity to human ACAT. Deletion of ARE2 reduced sterol ester levels to approximately 25 percent of normal levels, whereas disruption of ARE1 did not affect sterol ester biosynthesis. Deletion of both genes resulted in a viable cell with undetectable esterified sterol. Measurements of [$^{14}$C]acetate incorporation into saponified lipids indicated down-regulation of sterol biosynthesis in the are1 are2 mutant cells. With the use of a consensus sequence to the yeast and human genes, an additional member of the ACAT gene family was identified in humans.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.272.5266.1353