Saccharomyces cerevisiae MLF3/YNL074C gene, encoding a serine-rich protein of unknown function, determines the level of resistance to the novel immunosuppressive drug leflunomide

Abstract

The immunosuppressant leflunomide inhibits the growth of cytokine-stimulated proliferation of lymphoid cells in vitro and also inhibits the growth of the eukaryotic microorganism, Saccharomyces cerevisiae. To elucidate the molecular mechanism of action of the drug, a yeast gene which suppresses the anti-proliferative effect when in increased copy number was cloned and designated MLF3 for multicopy suppressor of leflunomide sensitivity. DNA sequencing analysis revealed that the MLF3 gene is identical to the YNL074C gene which encodes a serine-rich protein of 452 amino acids. Disruption of the MLF3 gene caused increased sensitivity to the immunosuppressant leflunomide.