title: Yeast bZip proteins mediate pleiotropic drug and metal resistance.
abstract: Saccharomyces cerevisiae contains a group of transcription factors related to mammalian c-Jun. This yeast Jun-family of proteins consists of GCN4, a regulator of genes involved in amino acid biosynthesis, and yAP-1, a factor conferring pleiotropic drug resistance when overexpressed. In the work described here, we show that a third member of the yeast Jun-family exists. This protein has been designated CAD1 and provides resistance to cadmium when present on a high-copy plasmid. CAD1 and yAP-1 are related in their amino-terminal DNA binding domains and can recognize the same DNA target site in vitro. Overproduction of CAD1 leads to transcriptional activation of an artificial reporter gene in delta yap1 cells. High level production of either CAD1 or yAP-1 causes cells to acquire a pleiotropic drug-resistant phenotype and to be able to tolerate normally toxic levels of iron chelators and zinc. Surprisingly, disruption of the CAD1 gene has no effect on the normal cellular resistance to cadmium but delta yap1 mutants are hypersensitive to this cytotoxic metal. The cadmium hypersensitivity of the delta yap1 mutant described here indicates that one major role of YAP1 in the yeast cell is to mediate resistance to this metal.
authors.affiliation: Program in Molecular Biology, University of Iowa, Iowa City 52242.
authors.forename: A
authors.initials: A
authors.lastname: Wu
authors.forename: J A
authors.initials: JA
authors.lastname: Wemmie
authors.forename: N P
authors.initials: NP
authors.lastname: Edgington
authors.forename: M
authors.initials: M
authors.lastname: Goebl
authors.forename: J L
authors.initials: JL
authors.lastname: Guevara
authors.forename: W S
authors.initials: WS
authors.lastname: Moye-Rowley
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D002104:Cadmium / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D004352:Drug Resistance, Microbial; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051790:G-Box Binding Factors; D015870:Gene Expression; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D009154:Mutation; D010940:Plant Proteins; D010957:Plasmids; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation; D015032:Zinc / Q000494:pharmacology
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C082904:CAD1 protein, S cerevisiae; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051790:G-Box Binding Factors; D010940:Plant Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D002104:Cadmium; D003513:Cycloheximide; D015032:Zinc