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Numerous ATP-binding cassette (ABC) proteins have been implicated in multidrug resistance, and some are also intimately connected to genetic diseases. For example, mammalian ABC proteins such as P-glycoproteins or multidrug resistance-associated proteins are associated with multidrug resistance phenomena (MDR), thus hampering anticancer therapy. Likewise, homologues in bacteria, fungi, or parasites are tightly associated with multidrug and antibiotic resistance. Several orthologues of mammalian MDR genes operate in the unicellular eukaryote Saccharomyces cerevisiae. Their functions have been linked to stress response, cellular detoxification, and drug resistance. This chapter discusses those yeast ABC transporters implicated in pleiotropic drug resistance and cellular detoxification. We describe strategies for their overexpression, biochemical purification, functional analysis, and a reconstitution in phospholipid vesicles, all of which are instrumental to better understanding their mechanisms of action and perhaps their physiological function.

Original publication

DOI

10.1016/S0076-6879(05)00026-1

Type

Chapter

Publication Date

2005

Volume

400

Pages

460 - 484

Keywords

ATP-Binding Cassette Transporters, Cell Membrane Structures, Cytoplasmic Vesicles, Drug Resistance, Multiple, Inactivation, Metabolic, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Structure-Activity Relationship, Up-Regulation