TY - JOUR
T1 - Membrane-active compounds activate the transcription factors Pdr1 and Pdr3 connecting pleiotropic drug resistance and membrane lipid homeostasis in Saccharomyces cerevisiae
AU - Schüller, Christoph
AU - Mamnun, Yasmine
AU - Wolfger, Hubert
AU - Rockwell, Nathan C.
AU - Thorner, Jeremy W.
AU - Kuchler, Karl
N1 - ***<REP_Import><OA_Full_2013>64438.28</OA_Full_2013></REP_Import>***
DOI: 10.1091/mbc.E07-06-0610
Coden: MBCEE
Source-File: 748Scopus210308.csv
Import aus Scopus: 2-s2.0-37049010139
Importdatum: 03.04.2008 13:12:04
15.01.2009: Datenanforderung 2652 (Import Sachbearbeiter)
09.02.2010: Datenanforderung UNIVIS-DATEN-DAT.RA-2 (Import Sachbearbeiter)
PY - 2007
Y1 - 2007
N2 - The Saccharomyces 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 activation of Pdr1 and Pdr3. Furthermore, Pdr1/Pdr3 target genes encoding the ATP-binding cassette proteins Pdr5 and Pdr15 confer resistance against these compounds. Genome-wide transcript analysis of wild-type and pdr1? pdr3? 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 is sufficient to confer regulation to a reporter gene by these substances in a Pdr1/Pdr3-dependent manner. Our data indicate that compounds with potential membrane-damaging or -perturbing effects might function as an activating signal for Pdr1 and Pdr3, and they suggest a role for their target genes in membrane lipid organization or remodeling. © 2007 by The American Society for Cell Biology.
AB - The Saccharomyces 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 activation of Pdr1 and Pdr3. Furthermore, Pdr1/Pdr3 target genes encoding the ATP-binding cassette proteins Pdr5 and Pdr15 confer resistance against these compounds. Genome-wide transcript analysis of wild-type and pdr1? pdr3? 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 is sufficient to confer regulation to a reporter gene by these substances in a Pdr1/Pdr3-dependent manner. Our data indicate that compounds with potential membrane-damaging or -perturbing effects might function as an activating signal for Pdr1 and Pdr3, and they suggest a role for their target genes in membrane lipid organization or remodeling. © 2007 by The American Society for Cell Biology.
M3 - Article
SN - 1059-1524
VL - 18
SP - 4932
EP - 4944
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 12
ER -