Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5

David J Katzmann, Timothy G. Hallstrom, Yannick Mahé, W. Scott Moye-Rowley

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)23049-23054
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number38
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Gene encoding
ATP-Binding Cassette Transporters
Response Elements
Binding Sites
Genes
Cycloheximide
Drug Resistance
Yeast
Proteins
Pharmaceutical Preparations
Zinc Fingers
Cell membranes
Gene expression
Saccharomyces cerevisiae
Zinc
Transcription Factors
Yeasts
Chemical activation
Maintenance
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry

Cite this

Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5. / Katzmann, David J; Hallstrom, Timothy G.; Mahé, Yannick; Scott Moye-Rowley, W.

In: Journal of Biological Chemistry, Vol. 271, No. 38, 1996, p. 23049-23054.

Research output: Contribution to journalArticle

@article{46b4cc068ec74771ad62221e44dde8a3,
title = "Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5",
abstract = "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.",
author = "Katzmann, {David J} and Hallstrom, {Timothy G.} and Yannick Mah{\'e} and {Scott Moye-Rowley}, W.",
year = "1996",
doi = "10.1074/jbc.271.38.23049",
language = "English (US)",
volume = "271",
pages = "23049--23054",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "38",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0029836129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029836129&partnerID=8YFLogxK

U2 - 10.1074/jbc.271.38.23049

DO - 10.1074/jbc.271.38.23049

M3 - Article

VL - 271

SP - 23049

EP - 23054

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 38

ER -