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Published August 3, 1989 | public
Journal Article

The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein


MAMMALIAN tumours displaying multidrug resistance overexpress a plasma membrane protein (P-glycoprotein), which is encoded by the MDR1 gene and apparently functions as an energy-dependent drug efflux pump. Tissue-specific expression of MDR1 and other members of the MDR gene family has been observed in normal cells, suggesting a role for P-glycoproteins in secretion. We have isolated a gene from the yeast Saccharomyces cerevisiae that encodes a protein very similar to mammalian P-glycoproteins. Deletion of this gene resulted in sterility of MATa, but not of MATα cells. Subsequent analysis revealed that the yeast P-glycoprotein is the product of the STE6 gene, a locus previously shown to be required in MATa cells for production of a-factor pheromone. Our findings suggest that the STE6 protein functions to export the hydrophobic a-factor lipopeptide in a manner analogous to the efflux of hydrophobic cytotoxic drugs catalysed by the related mammalian P-glycoprotein. Thus, the evolutionarily conserved family of MDR-like genes, including the hlyB gene of Escherichia coli and the STE6 gene of S. cerevisiae, encodes components of secretory pathways distinct from the classical, signal sequence-dependent protein translocation system.

Additional Information

© 1989 Nature Publishing Group. Received 15 May; accepted 26 June 1989. The nucleotide sequence data reported in this paper will appear in the EMBL, GenBank, and DDBJ Nucleotide Sequence Databases under the accession number Xl5428. We thank Richard Young for the yeast DNA libraries, Vivian Berlin for the sec and sst yeast strains, Catherine Nocente-McGrath for advice and photographic assistance, members of this laboratory, especially Mark Hochstrasser. for discussions, and Barbara Doran for secretarial assistance. This work was supported by grants to A. V. from the NIH. J.P.M. was supported in part by the Lucille P. Markey Charitable Trust.

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