Monitoring Editor: John York The S. cerevisiae zinc cluster transcription factors Pdr1 and Pdr3 mediate general drug resistance to many cytotoxic substances also known as pleiotropic drug resistance (PDR). The regulatory mechanisms that activate Pdr1 and Pdr3 in response to the various xenobiotics are poorly understood. In this study, we report that exposure of yeast cells to 2,4-dichlorophenol (DCP), benzyl alcohol, nonionic detergents, and lysophospholipids causes rapid induction of Pdr1 and Pdr3. Furthermore, Pdr1/Pdr3 target genes encoding the ABC proteins Pdr5 and Pdr15 confer resistance against these compounds. Genome-wide transcript analysis of wild type and pdr1Delta pdr3Delta cells treated with DCP reveals most prominently the activation of the PDR response but also other stress response pathways. Polyoxyethylene(9)laurylether treatment produced a similar profile with regard to activation of Pdr1 and Pdr3 suggesting activation of these by detergents. The Pdr1/Pdr3 response element (PDRE) is sufficient to confer regulation to a reporter gene by these substances in a Pdr1/Pdr3-dependent manner. Our data indicates that compounds with potential membrane-damaging or perturbing effects might function as an activating signal for Pdr1 and Pdr3 and suggest a role for their target genes in membrane lipid organization or remodelling.
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