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PMID:8360174

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Citation

Wu, A, Wemmie, JA, Edgington, NP, Goebl, M, Guevara, JL and Moye-Rowley, WS (1993) Yeast bZip proteins mediate pleiotropic drug and metal resistance. J. Biol. Chem. 268:18850-8

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.

Links

PubMed

Keywords

Amino Acid Sequence; Base Sequence; Basic-Leucine Zipper Transcription Factors; Binding Sites; Cadmium/pharmacology; Cycloheximide/pharmacology; DNA, Fungal/metabolism; DNA-Binding Proteins/physiology; Drug Resistance, Microbial; Fungal Proteins/chemistry; Fungal Proteins/genetics; Fungal Proteins/metabolism; G-Box Binding Factors; Gene Expression; Genes, Fungal; Molecular Sequence Data; Mutation; Plant Proteins; Plasmids; Recombinant Proteins/metabolism; Saccharomyces cerevisiae/chemistry; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription Factors/physiology; Transcriptional Activation; Zinc/pharmacology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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