Yeast adaptation to mancozeb involves the up-regulation of FLR1 under the coordinate control of Yap1, Rpn4, Pdr3, and Yrr1.
FLR1 gene, encoding a multidrug resistance (MDR) transporter of the major facilitator superfamily (MFS) was found to confer resistance to the fungicide mancozeb in Saccharomyces cerevisiae. This agrochemical has been linked to the development of Parkinson disease and cancer. Yeast response to mancozeb was proved to involve the strong activation of FLR1 transcription (20-fold) during the fungicide-induced growth latency. This activation of FLR1 transcription is fully dependent on Yap1p and is reduced (by 50%) in the absence of Rpn4p, Yrr1p or Pdr3p. A model for the coordinate action over FLR1 transcription activation, in response to mancozeb, of these transcription factors that mediate oxidative stress response (Yap1p), proteasome gene expression (Rpn4p), and pleiotropic drug resistance (Pdr3p and Yrr1p), is proposed.
Teixeira
Miguel Cacho
MC
IBB/CEBQ, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Dias
Paulo Jorge
PJ
Simões
Tânia
T
Sá-Correia
Isabel
I
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000502:physiology*; D005659:Fungicides, Industrial / Q000008:administration & dosage; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000502:physiology; D008344:Maneb / Q000008:administration & dosage*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D027361:Organic Anion Transporters; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D015038:Zineb / Q000008:administration & dosage*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C118429:FLR1 protein, S cerevisiae; D005659:Fungicides, Industrial; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; C089261:PDR3 protein, S cerevisiae; C119430:RPN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C477161:YBP1 protein, S cerevisiae; D008344:Maneb; C013099:mancozeb; D015038:Zineb