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Yeast bZip proteins mediate pleiotropic drug and metal resistance
Journal article   Open access   Peer reviewed

Yeast bZip proteins mediate pleiotropic drug and metal resistance

Ailing Wu, John A Wemmie, Nicholas P Edgington, Mark Goebl, Jose L Guevara and W Scott Moye-Rowley
The Journal of biological chemistry, Vol.268(25), pp.18850-18858
09/05/1993
DOI: 10.1016/S0021-9258(17)46705-6
PMID: 8360174
url
https://doi.org/10.1016/S0021-9258(17)46705-6View
Published (Version of record) Open Access

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

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