One of the most common origins of multidrug resistance occurs via the overproduction of ATP-binding cassette (ABC) transporter proteins. These ABC transporters then act as broad specificity drug pumps and efflux a wide range of toxic agents out of the cell. The yeast Saccharomyces cerevisiae exhibits multiple or pleiotropic drug resistance (Pdr) often through the overproduction of a plasma membrane-localized ABC transporter protein called Pdr5p. Expression of the PDR5 gene is controlled by two zinc cluster-containing transcription factors called Pdr1p and Pdr3p. Cells that lack their mitochondrial genome (0 cells) strongly induce PDR5 transcription in a Pdr3p-dependent fashion. To identify proteins associated with Pdr3p that might act to regulate this factor, a tandem affinity purification (TAP) moiety was fused to Pdr3p and this recombinant protein purified from yeast cells. The cytosolic Hsp70 chaperone Ssa1p co-purified with TAP-Pdr3p. Overexpression of Ssa1p repressed expression of PDR5 but had no effect on expression of other genes involved in the Pdr phenotype. This Ssa1p-mediated repression required the presence of Pdr3p and did not influence Pdr1p-dependent gene expression. Loss of the nucleotide exchange factor Fes1p mimicked Ssa1p-mediated repression of PDR5. Co-immunoprecipitation experiments indicated that Ssa1p was associated with Pdr3p but not Pdr1p in yeast cells. Finally, 0 cells had less Ssa1p bound to Pdr3p than + cells, consistent with Ssa1p-mediated repression of Pdr3p activity serving as a key regulatory step in control of multidrug resistance in yeast.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|