Yeast bZip proteins mediate pleiotropic drug and metal resistance

A. Wu, J. A. Wemmie, N. P. Edgington, M. Goebl, J. L. Guevara, W. S. Moye-Rowley

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161 Scopus citations

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 (US)
Pages (from-to)18850-18858
Number of pages9
JournalJournal of Biological Chemistry
Volume268
Issue number25
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    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.