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PMID: 18307995 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Compensatory activation of the multidrug transporters Pdr5p, Snq2p, and Yor1p by Pdr1p in Saccharomyces cerevisiae.

FEBS letters ·Vol. 582 ·No. 6 ·2008-03-19 ·Pages 977-83

Kolaczkowska A, Kolaczkowski M, Goffeau A, Moye-Rowley WS

Abstract

In Saccharomyces cerevisiae, the transcription factors Pdr1p and Pdr3p activate the expression of several genes, including PDR5, SNQ2, and YOR1, which encode ATP-binding cassette transporters that extrude dozens of antifungals with overlapping but distinct specificity. In this study, it was observed that growth resistance to specific Pdr5p substrates rose upon disruption of the YOR1 or SNQ2 coding region and was accompanied by increased efflux. Similarly, resistance to Yor1p- and Snq2p-specific substrates increased upon deletion of PDR5. The mRNA and protein levels of the respective transporters increased in parallel to drug resistance. beta-Galactosidase activity fused to the PDR5 or YOR1 promoter required the presence of Pdr1p and its specific binding sites for the compensatory induction, whereas Pdr3p had an inhibitory effect.

MeSH Terms
ATP-Binding Cassette Transporters/antagonists & inhibitors,genetics,metabolism Antifungal Agents/metabolism,pharmacology Azoles/metabolism,pharmacology Binding Sites DNA-Binding Proteins/genetics,metabolism Drug Resistance, Multiple, Fungal/genetics Gene Expression Regulation, Fungal Genes, Reporter Mitochondria/metabolism Promoter Regions, Genetic Protein Biosynthesis/genetics RNA, Messenger/metabolism Saccharomyces cerevisiae/drug effects,genetics,metabolism Saccharomyces cerevisiae Proteins/antagonists & inhibitors,genetics,metabolism Sequence Deletion Trans-Activators/genetics,metabolism Transcription Factors/metabolism Transcription, Genetic beta-Galactosidase/genetics
Chemicals
ATP-Binding Cassette Transporters Antifungal Agents Azoles DNA-Binding Proteins PDR1 protein, S cerevisiae PDR3 protein, S cerevisiae PDR5 protein, S cerevisiae RNA, Messenger SNQ2 protein, S cerevisiae Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors YOR1 protein, S cerevisiae beta-Galactosidase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kolaczkowska Anna
Faculty of Biotechnology, University of Wroclaw, ul. Tamka 2, 50-137 Wroclaw, Poland. [email protected] <[email protected]>
Kolaczkowski Marcin
Goffeau André
Moye-Rowley W Scott
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Article Info
Journal
FEBS letters
Abbr.
FEBS Lett
ISSN
0014-5793
DOI
10.1016/j.febslet.2008.02.045
Email
[email protected]
Published
2008-03-19
Epub
2008-00-26
Pages
977-83
Language
English
Region
England
NLM ID
0155157
PMCID
PMC2288637
Subset
IM
Grants
NIGMS NIH HHS · R01 GM049825 · United States
NIGMS NIH HHS · R01 GM049825-11 · United States
Intramural NIH HHS · United States
NIGMS NIH HHS · GM49825 · United States
External Links
PubMed source DOI: 10.1016/j.febslet.2008.02.045 PMC Full Text View journal details
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