title: Deletion of OSH3 gene confers resistance against ISP-1 in Saccharomyces cerevisiae.
abstract: Sphingolipids have been reported to regulate the growth and death of mammalian and yeast cells, but their precise mechanisms are unknown. In this paper, it was shown that the deletion of the oxysterol binding protein homologue 3 (OSH3) gene confers hyper resistance against ISP-1, an inhibitor of sphingolipid biosynthesis, in the yeast Saccharomyces cerevisiae. Furthermore, the overexpression of the ROK1 gene, which directly binds to Osh3p, conferred resistance against ISP-1, and the deletion of the KEM1 gene, which regulates microtubule functions, exhibited ISP-1 hypersensitivity. And yet, an ISP-1 treatment caused an abnormal mitotic spindle formation, and the ISP-1-induced cell cycle arrest was rescued by the deletion of the OSH3 gene. Taken together, it is suggested that the expression levels of the OSH3 gene influence the ISP-1 sensitivity of S. cerevisiae, and the sphingolipids are necessary for normal mitotic spindle formation in which the Osh3p may play a pivotal role.
authors.affiliation: Lead Discovery Research Laboratories, SANKYO CO., LTD., 2-58, Hiromachi 1, Shinagawa-Ku, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yano
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inukai
authors.forename: Fujio
authors.initials: F
authors.lastname: Isono
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D053487:DEAD-box RNA Helicases; D025141:Drug Resistance, Fungal; D005095:Exoribonucleases / Q000235:genetics; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics; D017353:Gene Deletion; D005800:Genes, Fungal; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D013107:Sphingolipids / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D002352:Carrier Proteins; D005229:Fatty Acids, Monounsaturated; C432936:OSH3 protein, S cerevisiae; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D005095:Exoribonucleases; C068398:XRN1 protein, S cerevisiae; C120858:ROK1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases; C001996:thermozymocidin