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

Nature. 1989 Aug 3;340(6232):400-4. doi: 10.1038/340400a0.

Abstract

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 MAT alpha 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters*
  • Amino Acid Sequence
  • Base Sequence
  • Drug Resistance / genetics*
  • Escherichia coli / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genes, Bacterial
  • Genes, Fungal*
  • Glycoproteins*
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Molecular Sequence Data
  • Mutation
  • Pheromones / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Nucleic Acid

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Fungal Proteins
  • Glycoproteins
  • Membrane Glycoproteins
  • Pheromones
  • STE6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins

Associated data

  • GENBANK/X15428