Yeast ATP-binding cassette transporters: cellular cleaning pumps.
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.
Ernst
Robert
R
Institute of Biochemistry, Membrane Transport Group, Heinrich-Heine University of Düsseldorf, Germany.
Klemm
Robin
R
Schmitt
Lutz
L
Kuchler
Karl
K
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000502:physiology*; D022162:Cytoplasmic Vesicles / Q000737:chemistry; D018432:Drug Resistance, Multiple; D008658:Inactivation, Metabolic; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015854:Up-Regulation
D018528:ATP-Binding Cassette Transporters; D029701:Saccharomyces cerevisiae Proteins