The Immunosuppressant SR 31747 Blocks Cell Proliferation by Inhibiting a Steroid Isomerase in Saccharomyces cerevisiae
Autor: | Daniel Caput, G Le Fur, A Rahier, Mourad Kaghad, C Lanau, P.-H. Dupuy, M Taton, Gérard Loison, Claudine Picard, A Josse, Pascal Leplatois, P. Ferrara, C Dhers, Sandra Silve |
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Rok vydání: | 1996 |
Předmět: |
Isomerase activity
Genes Fungal Molecular Sequence Data Mutant Saccharomyces cerevisiae Gene Expression Steroid Isomerases Isomerase Biology Fungal Proteins Gene product chemistry.chemical_compound Transformation Genetic Cyclohexanes Ergosterol polycyclic compounds Amino Acid Sequence Enzyme Inhibitors Molecular Biology Sequence Homology Amino Acid Cell growth Drug Resistance Microbial Cell Biology biology.organism_classification Sterol chemistry Biochemistry Mutation lipids (amino acids peptides and proteins) Cell Division Gene Deletion Immunosuppressive Agents Research Article |
Zdroj: | Molecular and Cellular Biology. 16:2719-2727 |
ISSN: | 1098-5549 |
DOI: | 10.1128/mcb.16.6.2719 |
Popis: | SR 31747 is a novel immunosuppressant agent that arrests cell proliferation in the yeast Saccharomyces cerevisiae, SR 31747-treated cells accumulate the same aberrant sterols as those found in a mutant impaired in delta 8- delta 7-sterol isomerase. Sterol isomerase activity is also inhibited by SR 31747 in in vitro assays. Overexpression of the sterol isomerase-encoding gene, ERG2, confers enhanced SR resistance. Cells growing anaerobically on ergosterol-containing medium are not sensitive to SR. Disruption of the sterol isomerase-encoding gene is lethal in cells growing in the absence of exogenous ergosterol, except in SR-resistant mutants lacking either the SUR4 or the FEN1 gene product. The results suggest that sterol isomerase is the target of SR 31747 and that both the SUR4 and FEN1 gene products are required to mediate the proliferation arrest induced by ergosterol depletion. |
Databáze: | OpenAIRE |
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