Kolaczkowska Anna, Kolaczkowski Marcin, Goffeau André, Moye-Rowley W Scott
Faculty of Biotechnology, University of Wroclaw, ul. Tamka 2, 50-137 Wroclaw, Poland.
FEBS Lett. 2008 Mar 19;582(6):977-83. doi: 10.1016/j.febslet.2008.02.045. Epub 2008 Feb 26.
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.
在酿酒酵母中，转录因子Pdr1p和Pdr3p激活多个基因的表达，包括PDR5、SNQ2和YOR1，这些基因编码ATP结合盒转运蛋白，可排出数十种具有重叠但不同特异性的抗真菌药物。在本研究中，观察到破坏YOR1或SNQ2编码区后，对特定Pdr5p底物的生长抗性增强，并伴有外排增加。同样，缺失PDR5后，对Yor1p和Snq2p特异性底物的抗性增加。各转运蛋白的mRNA和蛋白质水平与耐药性平行增加。与PDR5或YOR1启动子融合的β-半乳糖苷酶活性需要Pdr1p及其特异性结合位点的存在才能进行代偿性诱导，而Pdr3p具有抑制作用。
