TY - JOUR
T1 - Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5
AU - Katzmann, David J.
AU - Hallstrom, Timothy G.
AU - Mahé, Yannick
AU - Scott Moye-Rowley, W.
PY - 1996
Y1 - 1996
N2 - Saccharomyces cerevisiae has large number of genes that can be genetically altered to produce a multiple or pleiotropic drug resistance phenotype. The homologous zinc finger transcription factors Pdr1p and Pdr3p both elevate resistance to many drugs, including cycloheximide. This elevation in cycloheximide tolerance only occurs in the presence of an intact copy of the PDR5 gene that encodes a plasma membrane-localized ATP binding cassette transporter protein. Previously, we have found that a single binding site for Pdr3p present in the PDR5 promoter is sufficient to provide Pdr3p- responsive gene expression. In this study, we have found that there are three sites in the PDR5 5'-noncoding region that are closely related to one another and are bound by both Pdr1p and Pdr3p. These elements have been designated Pdr1p/Pdr3p response elements (PDREs), and their role in the maintenance of normal PDR5 expression has been analyzed. Mutations have been constructed in each PDRE and shown to eliminate Pdr1p/Pdr3p binding in vitro. Analysis of the effect of these mutant PDREs on normal PDR5 promoter function indicates that each element is required for wildtype expression and drug resistance. A single PDRE placed upstream of a yeast gene lacking its normal upstream activation sequence is sufficient to confer Pdr1p responsiveness to this heterologous promoter.
AB - Saccharomyces cerevisiae has large number of genes that can be genetically altered to produce a multiple or pleiotropic drug resistance phenotype. The homologous zinc finger transcription factors Pdr1p and Pdr3p both elevate resistance to many drugs, including cycloheximide. This elevation in cycloheximide tolerance only occurs in the presence of an intact copy of the PDR5 gene that encodes a plasma membrane-localized ATP binding cassette transporter protein. Previously, we have found that a single binding site for Pdr3p present in the PDR5 promoter is sufficient to provide Pdr3p- responsive gene expression. In this study, we have found that there are three sites in the PDR5 5'-noncoding region that are closely related to one another and are bound by both Pdr1p and Pdr3p. These elements have been designated Pdr1p/Pdr3p response elements (PDREs), and their role in the maintenance of normal PDR5 expression has been analyzed. Mutations have been constructed in each PDRE and shown to eliminate Pdr1p/Pdr3p binding in vitro. Analysis of the effect of these mutant PDREs on normal PDR5 promoter function indicates that each element is required for wildtype expression and drug resistance. A single PDRE placed upstream of a yeast gene lacking its normal upstream activation sequence is sufficient to confer Pdr1p responsiveness to this heterologous promoter.
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U2 - 10.1074/jbc.271.38.23049
DO - 10.1074/jbc.271.38.23049
M3 - Article
C2 - 8798494
AN - SCOPUS:0029836129
SN - 0021-9258
VL - 271
SP - 23049
EP - 23054
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 38
ER -