Preface: the concept and consequences of multidrug resistance.
The problem of multidrug resistance (MDR) in human cancers led to the discovery 30 years ago of a single protein P-glycoprotein (P-gp), capable of mediating resistance to multiple structurally diverse drugs. P-gp became the archetypal eukaryotic ABC transporter gene, and studies of P-gp and related ABC transporters in both eukaryotes and bacteria have led to a basic mechanistic understanding of the molecular basis of MDR. Particular milestones along the way have been the identification of the homology between P-gp and bacterial transport proteins, the purification and functional reconstitution of P-gp into synthetic lipid systems, and the development of targeted therapies that attempt to overcome MDR by inhibiting P-gp. This preface places into this context some of the less well-explored themes developed in the MDR field, particularly various alternative models of P-gp action, evidence for parallel physiological roles for P-gp, and the unusual relationship between the substrate recognition capabilities of ABC transporters and their evolutionary history.
Sheps
Jonathan A
JA
BC Cancer Research Centre, Vancouver, British Columbia, Canada. vling@bccrc.ca
Ling
Victor
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005075:Biological Evolution; D018432:Drug Resistance, Multiple / Q000235:genetics; D006460:Hemolysin Proteins / Q000502:physiology; D006801:Humans; D008051:Lipid Bilayers
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D006460:Hemolysin Proteins; D008051:Lipid Bilayers; D000255:Adenosine Triphosphate; C086257:hemolysin B