Effect of ATP binding cassette/multidrug resistance proteins on ATP efflux of Saccharomyces cerevisiae.

Multidrug resistance (MDR) in mammalian tumors or tissues is often associated with the overexpression of the putative drug efflux pump P-glycoprotein (Pgp). One theory concerning the mechanism of Pgp activity is that efflux of ATP is coupled to drug efflux. Evidence in support of this theory has been observed in mammalian cells. Recently, the STS1 gene, which is a multidrug resistance gene related to the mammalian Pgp's, has been characterized in S. cerevisiae. Also, the mouse mdr3 Pgp has been functionally expressed in yeast cells. Therefore, it was of interest to determine whether the expression of these proteins affected ATP efflux from yeast. Although both genes were shown to confer MDR, thus confirming functional expression, the endogenous glucose-dependent, drug-stimulated ATP efflux activity of yeast was not affected by expression of STS1, and was decreased by the expression of mouse mdr3.