EFFECT OF ATP BINDING CASSETTE MULTIDRUG RESISTANCE PROTEINS ON ATP EFFLUX OF SACCHAROMYCES-CEREVISIAE/

Multidrug resistance (MDR) in mammalian tumors or tissues is often ass ociated with the overexpression of the putative drug efflux pump P-gly coprotein (Pgp). One theory concerning the mechanism of Pgp activity i s 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 Pg p'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 affecte d ATP efflux from yeast. Although both genes were shown to confer MDR, thus confirming functional expression, the endogenous glucose-depende nt, drug-stimulated ATP efflux activity of yeast was not affected by e xpression of STS1, and was decreased by the expression of mouse mdr3. (C) 1997 Academic Press