Mutations in the yeast PDR3, PDR4, PDR7 and PDR9 pleiotropic (multiple) drug resistance loci affect the transcript level of an ATP binding cassette transporter encoding gene, PDR5.

Abstract

The yeast pleiotropic (multiple drug) resistance gene PDR5 encodes a product with homology to a large number of membrane transport proteins including the mammalian multiple drug resistance family. In this study, we identified four genes on chromosome II that affect the steady-state level of PDR5 transcript in addition to a previously identified positive regulator, PDR1. The genes in question are PDR3, PDR4, PDR7 and PDR9. We also analyzed the interaction between PDR5 and YAP1. YAP1 encodes a positive regulator with a leucine zipper motif that causes pleiotropic drug resistance when overproduced. YAP1-mediated pleiotropic drug resistance is not dependent on the presence of PDR5 and must act through other genes.

In Vitro Bioassays for Assessing Estrogenic Substances

“…Other receptor-mediated yeast-based assays have also reported different ligand potencies when compared to mammalian counterparts (153,171,172). Factors such as cell wall permeability, variations in S. cerevisiae strains, differences in receptor levels and protein proteolysis mechanisms, non-receptor cell-specific factors, metabolic capabilities, multidrug resistance efflux pumps, and endogenous yeast binding proteins have been suggested as possible explanations for these differences (153,165,169,171,(173)(174)(175). Consequently, assessments conducted using yeast require confirmation in other in vitro and in vivo assays.…”