Yap1p, a yeast transcriptional activator that mediates multidrug resistance, regulates the metabolic stress response

EMBO J. 1994 Sep 1;13(17):4036-41.

Abstract

Overexpression of the YAP1 transcriptional activator renders yeast cells resistant to multiple metabolic inhibitors. In an effort to identify other gene products required for this phenotype we have isolated genomic mutations which neutralize this effect. One such mutation was further characterized and the affected gene was shown to be identical to TPS2 which encodes trehalose phosphate phosphatase, an enzyme catalysing the second step in trehalose biosynthesis. We have analysed the transcriptional regulation of the TPS2 gene and have shown that its transcription is induced by a variety of stressful conditions caused by metabolic inhibitors, osmotic shock and heat shock. This transcriptional activation is mediated by multiple stress promoter elements (C4T) and requires the function of Yap1p as well as reduced activity of the cAMP-regulated protein kinase. Using an appropriate reporter gene we have shown that Yap1p is generally required for transcriptional regulation through the C4T stress element. These results show that the YAP1 protein has a pivotal role in the metabolic stress response and the acquisition of stress tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological / genetics
  • Base Sequence
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / metabolism*
  • Drug Resistance, Microbial / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal*
  • Genes, Fungal / genetics
  • Glucosyltransferases / biosynthesis*
  • Glucosyltransferases / genetics*
  • Heat-Shock Proteins / biosynthesis
  • Hot Temperature
  • Molecular Sequence Data
  • Multienzyme Complexes / biosynthesis*
  • Multienzyme Complexes / genetics*
  • Phosphoric Monoester Hydrolases / biosynthesis*
  • Phosphoric Monoester Hydrolases / genetics*
  • Promoter Regions, Genetic / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction
  • Transcription Factors / metabolism*
  • Trehalose / biosynthesis

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • Heat-Shock Proteins
  • Multienzyme Complexes
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • YAP1 protein, S cerevisiae
  • Trehalose
  • Glucosyltransferases
  • trehalose-6-phosphate synthase-phosphatase complex
  • Cyclic AMP-Dependent Protein Kinases
  • Phosphoric Monoester Hydrolases