Transcriptional activation mediated by the yeast AP-1 protein is required for normal cadmium tolerance

J Biol Chem. 1994 May 20;269(20):14690-7.


The yeast YAP1 gene encodes a transcriptional regulatory protein that utilizes a basic region-leucine zipper (bZip) DNA-binding domain to recognize its cognate DNA element. A synthetic reporter gene containing a SV40 AP-1 response element (ARE) cloned upstream of a TRP5 promoter-lacZ gene fusion shows yAP-1-dependent transactivation in vivo. Recent work has shown that changes in the gene dosage of this factor can dramatically alter the ability of a cell to tolerate a host of toxic agents including cadmium, cycloheximide, and sulfometuron methyl. We have focused on the YAP1-dependent cadmium resistance as cells that lack a functional YAP1 gene are hypersensitive to this metal. Deletion mapping experiments define two domains in the carboxyl-terminal region of the yAP-1 protein that are required for normal cadmium tolerance and ARE-TRP5-lacZ expression. Single amino acid substitutions in the bZip domain of yAP-1 indicate that this region is required for normal DNA binding and in vivo function of the protein. Replacement of a non-canonical asparagine with leucine in the yAP-1 leucine zipper leads to production of a defective protein. A substitution mutation in the basic domain converts this mutant protein into a dominant negative factor. The ability of yAP-1 to act as a positive regulator of transcription is required for its biological action.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Blotting, Western
  • Cadmium / toxicity*
  • Cycloheximide / toxicity
  • DNA Primers
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Drug Resistance, Microbial / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal* / drug effects
  • Genes, Fungal*
  • Molecular Sequence Data
  • Mutagenesis
  • Phenotype
  • Plasmids
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Deletion
  • Sulfonylurea Compounds / toxicity
  • Transcription Factors / biosynthesis
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transcriptional Activation
  • beta-Galactosidase / biosynthesis


  • DNA Primers
  • DNA-Binding Proteins
  • Fungal Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Sulfonylurea Compounds
  • Transcription Factors
  • YAP1 protein, S cerevisiae
  • Cadmium
  • Cycloheximide
  • beta-Galactosidase
  • sulfometuron methyl