The yeast zinc finger regulators Pdr1p and Pdr3p control pleiotropic drug resistance (PDR) as homo- and heterodimers in vivo

Mol Microbiol. 2002 Dec;46(5):1429-40. doi: 10.1046/j.1365-2958.2002.03262.x.


The transcription factors Pdr1p and Pdr3p from Saccharomyces cerevisiae mediate pleiotropic drug resistance (PDR) by controlling expression of ATP-binding cassette (ABC) transporters such as Pdr5p, Snq2p and Yor1p. Previous in vitro studies demonstrated that Pdr1p and Pdr3p recognize so-called pleiotropic drug resistance elements (PDREs) in the promoters of target genes. In this study, we show that both Pdr1p and Pdr3p are phosphoproteins; Pdr3p isoforms migrate as two bands in gel electrophoresis, reflecting two distinct phosphorylation states. Most importantly, native co-immunoprecipitation experiments, using functional epitope-tagged Pdr1p/Pdr3p variants, demonstrate that Pdr1p and Pdr3p can form both homo- and heterodimers in vivo. Furthermore, in vivo footprinting of PDRE-containing promoters demonstrate that Pdr1p/Pdr3p constitutively occupy both perfect and degenerate PDREs in vivo. Thus, in addition to interaction with other regulators, differential dimerization provides a plausible explanation for the observation that Pdr3p and Pdr1p can both positively and negatively control PDR promoters with different combinations of perfect and degenerate PDREs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • DNA Footprinting
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Drug Resistance, Multiple, Fungal / genetics*
  • Gene Expression Regulation, Fungal*
  • Promoter Regions, Genetic / genetics
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Zinc Fingers


  • ATP-Binding Cassette Transporters
  • DNA-Binding Proteins
  • PDR1 protein, S cerevisiae
  • PDR3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors