Yeast bZip proteins mediate pleiotropic drug and metal resistance

Ailing Wu, John A. Wemmie, Nicholas P. Edgington, Mark Goebl, Jose L. Guevara, W. Scott Moye-Rowley

Research output: Contribution to journalArticle

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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 Δyap1 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 Δyap1 mutants are hypersensitive to this cytotoxic metal. The cadmium hypersensitivity of the Δyap1 mutant described here indicates that one major role of YAP1 in the yeast cell is to mediate resistance to this metal.

Original languageEnglish
Pages (from-to)18850-18858
Number of pages9
JournalJournal of Biological Chemistry
Volume268
Issue number25
StatePublished - Sep 5 1993

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Fungal Proteins
Cadmium
Drug Resistance
Yeast
Yeasts
Metals
Genes
Pharmaceutical Preparations
Synthetic Genes
Poisons
DNA
Regulator Genes
Chelating Agents
Reporter Genes
Transcriptional Activation
Saccharomyces cerevisiae
Zinc
Biosynthesis
Hypersensitivity
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Wu, A., Wemmie, J. A., Edgington, N. P., Goebl, M., Guevara, J. L., & Moye-Rowley, W. S. (1993). Yeast bZip proteins mediate pleiotropic drug and metal resistance. Journal of Biological Chemistry, 268(25), 18850-18858.

Yeast bZip proteins mediate pleiotropic drug and metal resistance. / Wu, Ailing; Wemmie, John A.; Edgington, Nicholas P.; Goebl, Mark; Guevara, Jose L.; Moye-Rowley, W. Scott.

In: Journal of Biological Chemistry, Vol. 268, No. 25, 05.09.1993, p. 18850-18858.

Research output: Contribution to journalArticle

Wu, A, Wemmie, JA, Edgington, NP, Goebl, M, Guevara, JL & Moye-Rowley, WS 1993, 'Yeast bZip proteins mediate pleiotropic drug and metal resistance', Journal of Biological Chemistry, vol. 268, no. 25, pp. 18850-18858.
Wu A, Wemmie JA, Edgington NP, Goebl M, Guevara JL, Moye-Rowley WS. Yeast bZip proteins mediate pleiotropic drug and metal resistance. Journal of Biological Chemistry. 1993 Sep 5;268(25):18850-18858.
Wu, Ailing ; Wemmie, John A. ; Edgington, Nicholas P. ; Goebl, Mark ; Guevara, Jose L. ; Moye-Rowley, W. Scott. / Yeast bZip proteins mediate pleiotropic drug and metal resistance. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 25. pp. 18850-18858.
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