The multidrug resistance-associated protein (MRP) subfamily (Yrs1/Yor1) of Saccharomyces cerevisiae is important for the tolerance to a broad range of organic anions.
We have cloned and characterized a Saccharomyces cerevisiae gene YRS1 that complements the phenotype of the mutant sensitive to the anionic drug reveromycin A. The YRS1 gene, which is identical to the recently identified YOR1 gene, encodes a protein with extensive homology to the human multidrug resistance-associated protein (MRP) and the yeast cadmium factor (Ycf1). A chromosomal deletion of YRS1 lead to viable Deltayrs1 cells, which exhibited hypersensitivity to reveromycin A. Elevation of the YRS1 gene dosage in wild type cells conferred increased resistance to reveromycin A. By analyzing the effect of YRS1 disruption and overexpression it was demonstrated that Yrs1 is involved in the detoxification of a wide range of the organic anions that contain carboxyl group(s) but none of the other type of toxic compounds examined. Fluorescence-activated cell sorter analysis indicated the increased accumulation of the anionic fluorescent compound rhodamine B in Deltayrs1 cells. The expression of YRS1 was induced strikingly by reveromycin A. These results suggest that Yrs1 is a multispecific organic anion transporter important for tolerance against toxic environmental organic anions. Yrs1 had an overlapping specificity with Ycf1 in the resistance to cadmium.
Cui
Z
Z
Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, Higashi-Hiroshima 739, Japan.
Hirata
D
D
Tsuchiya
E
E
Osada
H
H
Miyakawa
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000838:Anions / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005456:Fluorescent Dyes; D015870:Gene Expression; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006801:Humans; D008826:Microbial Sensitivity Tests; D005810:Multigene Family; D016296:Mutagenesis; D010641:Phenotype; D011714:Pyrans / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012235:Rhodamines / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013141:Spiro Compounds / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000838:Anions; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D005456:Fluorescent Dyes; D011714:Pyrans; D011994:Recombinant Proteins; D012235:Rhodamines; D029701:Saccharomyces cerevisiae Proteins; D013141:Spiro Compounds; C097077:YOR1 protein, S cerevisiae; C068098:reveromycin A; C029773:rhodamine B