In yeast, broad-spectrum resistance inhibitors is mediated by a series of membrane transporters that are members of the ABC superfamily and use ATP to power drug efflux. The genes involved include PDR5, YOR1, and SNQ2. These loci are in turn regulated by zinc cluster transcriptionfactors encoded by the PDR1, YRR1 (PDR2) and PDR3 genes. Dominant gain-of-function mutations in PDR2 cause hyper-resistance via the over expression of YOR1, SNQ2 and at least one other target. Curiously, this target requires the presence of the Ubp6 ubiquitin hydrolase. Null mutations in UBP6 create hypersensitivity to inhibitors of protein translation. Using microarray analysis, the Ubp6-dependent PDR2 target will be identified. Subsequent genetic analysis will identify other genes that work along with UBP6. This work, along with some simple molecular cytology should help determine the precise role of this hydrolase in the cell.
| Golin, John; Ambudkar, Suresh V; May, Leopold (2007) The yeast Pdr5p multidrug transporter: how does it recognize so many substrates? Biochem Biophys Res Commun 356:1-5 |
