The Saccharomyces cerevisiae MLF6/YPL244C gene, which encodes a possible yeast homologue of mammalian UDP-galactose transporter, confers resistance to the immunosuppressive drug, leflunomide.
The immunosuppressant leflunomide (LFM) inhibits the growth of cytokine-stimulated proliferation of lymphoid cells in vitro and also inhibits the growth of eukaryotic microorganism, Saccharomyces cerevisiae. As a first step to elucidate the molecular mechanism of LFM action in human, yeast gene which suppresses the anti-proliferative effect when in increased copy number was cloned and designated MLF6 for multicopy suppressor of LFM sensitivity. DNA sequencing analysis revealed that the MLF6 gene is identical to the YPL244C gene which encodes a possible yeast homologue of human UDP-galactose transporter. The disruption of the MLF6 gene increased the sensitivity of yeast cells to the drug.
Fujimura
H
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Laboratory of Advanced Technology, Discovery Research Laboratories, Nippon Hoechst Marion Roussel, 1-3-2 Minamidai, Kawagoe 350-1165, Japan. Fujimura.Hiroaki@organon.co.jp
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology; D001692:Biological Transport; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D005800:Genes, Fungal; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D014531:Uridine Diphosphate Galactose / Q000378:metabolism; D000099237:UDP-Galactose Translocators
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D000077339:Leflunomide; D009004:Monosaccharide Transport Proteins; D014531:Uridine Diphosphate Galactose; D000099237:UDP-Galactose Translocators