Characterization of a family of yeast transcriptional regulators : the zine cluster proteins

Members of the zinc cluster (or binuclear cluster) protein family are characterized by a Zn(II)Cys6 zinc finger involved in DNA recognition and binding. These fungal proteins are transcriptional regulators of genes involved in a wide variety of cellular processes. One member, Gal4p, is involved in galactose metabolism, while others play a major role in primary and secondary metabolism, control of meiosis, and multidrug resistance. Sequencing of the Saccharomyces cerevisiae genome has revealed that 55 genes encoding putative zinc cluster proteins are present in budding yeast. However, the roles of many of these zinc cluster proteins are unknown. In order to better understand their functions, we have performed a phenotypic analysis of these putative zinc cluster proteins. We have implicated a number of them in a variety of processes in the cell, including multidrug resistance. Stb5p has been shown to be a major player in regulating the expression of multidrug resistance genes. Other zinc cluster activators of multidrug resistance genes include Pdr1p, Pdr3p, and Yrr1p. These regulators of multidrug resistance appear to interact with each other, forming many different sub-populations of homo- and heterodimers. Stb5p is found predominantly as a heterodimer with Pdr1p. It also appears that Pdr1p is a master regulator able to interact with many different partners, enabling it to mediate control over multidrug resistance genes