Multiple interfaces control activity of the Candida glabrata Pdr1 transcription factor mediating azole drug resistance

The Cys(6)Zn(2) DNA-binding domain transcription factor Pdr1 is a central regulator of drug resistance in the pathogenic yeast Candida glabrata. In this review, I discuss the multiple control mechanisms modulating the function of this positive transcriptional regulator. Available data suggest that Pdr1 activity is restrained by multiple negative inputs that can be lost by either mutagenesis of the protein or loss of trans-acting factors. Although extensive data are available on the C. glabrata transactivator as well as its cognate proteins in Saccharomyces cerevisiae, the physiological rationale underlying the regulation of these factors remains to be understood.