title: Pradimicin resistance of yeast is caused by a mutation of the putative N-glycosylation sites of osmosensor protein Sln1.
abstract: Pradimicin, a mannose-binding antifungal antibiotic, induces apoptosis-like cell death in Saccharomyces cerevisiae. Previously we found that the substitution of the 74th amino acid from glycine to cysteine in Ypd1 yields a mutant resistant to pradimicin. In this study, the involvement of a membrane-spanning osomosensor, Sln1, which is located upstream of Ypd1, was investigated. A mutant, sln1 DeltaNG, that lacks the putative N-glycosylation sites in the extracellular domain became resistant to pradimicin. On the other hand, the null mutants of Ssk1, Pbs2, and Hog1, which are located downstream of the Sln1 cascade, were sensitive to pradimicin as well as the wild-type strain. In conclusion, pradimicin exerts its fungicidal action with the involvement of Sln1, but the downstream branch, Ssk1 and the HOG pathway, is not involved.
authors.affiliation: Biotechnology Research Center, Toyama Prefectural University, Toyama, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Hiramoto
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nomura
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Furumai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Oki
mesh_terms: D000595:Amino Acid Sequence; D018943:Anthracyclines / Q000378:metabolism / Q000494:pharmacology*; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D025141:Drug Resistance, Fungal / Q000235:genetics*; D006031:Glycosylation; D047908:Intracellular Signaling Peptides and Proteins; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D018943:Anthracyclines; D000935:Antifungal Agents; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C083749:SLN1 protein, S cerevisiae