title: Characterization of a novel Schizosaccharomyces pombe multidrug resistance transporter conferring brefeldin A resistance.
abstract: Brefeldin A disrupts protein secretion and causes the redistribution of the Golgi complex to endoplasmic reticulum in both mammalian cells and wild type Schizosaccharomyces pombe. We have previously isolated six different genes that, when present in multiple copies, confer brefeldin A resistance to wild type S. pombe. Here we present the characterization of one of these genes, hba2, which encodes a novel S. pombe protein that shares significant sequence similarity to members of the ATP-binding cassette superfamily of transport proteins. Examination of hba2 expression determined that this gene is overexpressed in mutant strains resistant to brefeldin A due to mutations in the negative regulator crm1 (bar1) gene or the bar2 gene. The increase of hba2 expression was independent of the pap1 transcription factor which is repressed by wild type crm1. These results suggest that crm1 negatively regulates multiple transcription factors including one that modulates hba2 transcription.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Turi
authors.forename: J K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D020126:Brefeldin A; D003001:Cloning, Molecular; D003517:Cyclopentanes / Q000494:pharmacology*; D004271:DNA, Fungal / Q000737:chemistry*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D000073718:Pancreatitis-Associated Proteins; D015183:Restriction Mapping; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins; D017421:Sequence Analysis; D017385:Sequence Homology
chemical_list: D018528:ATP-Binding Cassette Transporters; C092496:BFR1 protein, S pombe; D003517:Cyclopentanes; D004271:DNA, Fungal; D005656:Fungal Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D029702:Schizosaccharomyces pombe Proteins; D020126:Brefeldin A; D000255:Adenosine Triphosphate