Boyum R, Guidotti G
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Biochem Biophys Res Commun. 1997 Jan 3;230(1):22-6. doi: 10.1006/bbrc.1996.5913.
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.
哺乳动物肿瘤或组织中的多药耐药性（MDR）通常与假定的药物外排泵P-糖蛋白（Pgp）的过表达有关。一种关于Pgp活性机制的理论是，ATP的外排与药物外排相偶联。在哺乳动物细胞中已观察到支持该理论的证据。最近，与哺乳动物Pgp相关的多药耐药基因STS1已在酿酒酵母中得到表征。此外，小鼠mdr3 Pgp已在酵母细胞中实现功能性表达。因此，确定这些蛋白质的表达是否影响酵母中的ATP外排很有意义。尽管两个基因均显示可赋予MDR，从而证实了功能性表达，但酵母内源性葡萄糖依赖性、药物刺激的ATP外排活性不受STS1表达的影响，而受小鼠mdr3表达的降低。
