The effects of transcription regulating genes PDR1, pdr1-3 and PDR3 in pleiotropic drug resistance.

Mutations in the yeast PDR1 or PDR3 genes lead to acquisition of resistance towards various unrelated cytotoxic compounds. The broad range and different properties of these compounds indicate the existence of mechanisms which protect cellular targets, neutralise or expel the compounds from the cell. In wild type and pdr mutants, 83 proteins, out of 2706 detected by two-dimensional gel electrophoresis, were differentially expressed. Fifty-three of these could be identified by mass spectrometry. The functions of these 53 proteins fall into several metabolic groups demonstrating that drug resistance phenotype is a mosaic response derived from such diverse functions as stress defence, endocytosis, oxidation and reduction, amino acid synthesis and mitochondrial biogenesis. The patterns of synthesis of the selected proteins clearly demonstrates the complex interaction between Pdr1p and Pdr3p in exerting their regulatory functions. The data also indicate that, in the Saccharomyces cerevisiae pleiotropic drug resistance phenomenon, translational events exert a more decisive effect than transcription in regulating the levels of active forms of the proteins involved.