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Heterologous expression systems for P-glycoprotein:E. coli, yeast, and baculovirus

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Abstract

Chemotherapy, though it remains one of the front-line weapons used to treat human cancer, is often ineffective due to drug resistance mechanisms manifest in tumor cells. One common pattern of drug resistance, characterized by simultaneous resistance to multiple amphipathic, but otherwise structurally dissimilar anticancer drugs, is termed multidrug resistance. Multidrug resistance in various model systems, covering the phylogenetic range from bacteria to man, can be conferred by mammalian P-glycoproteins (PGPs), often termed multidrug transporters. PGPs are 170-kD polytopic membrane proteins, predicted to consist of two homologous halves, each with six membrane spanning regions and one ATP binding site. They are members of the ATP-binding cassette (ABC) superfamily of transporters, and are known to function biochemically as energy-dependent drug efflux pumps. However, much remains to be learned about PGP structure-function relationships, membrane topology, posttranslational regulation, and bioenergetics of drug transport. Much of the recent progress in the study of the human and mouse PGPs has come from heterologous expression systems which offer the benefits of ease of genetic selection and manipulation, and/or short generation times of the organism in which PGPs are expressed, and/or high-level expression of recombinant PGP. Here we review recent studies of PGP inE. coli, baculovirus, and yeast systems and evaluate their utility for the study of PGPs, as well as other higher eukaryotic membrane proteins.

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Author notes

  1. David Chen

    Present address: Interinstitute Medical Genetics Program, and Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, 20892, Bethesda, Maryland

  2. Ursula A. Germann

    Present address: Vertex Pharmaceuticals, 02139, Cambridge, Massachusetts

Authors and Affiliations

  1. Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 37 Convent DR MSC 4255, 20892-4255, Bethesda, Maryland

    Gregory L. Evans, David Chen & Ira Pastan

  2. Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, 37, Convent DR MSC 4255, 20892-4255, Bethesda, Maryland

    Baofu Ni, Christine A. Hrycyna, Ursula A. Germann & Michael M. Gottesman

  3. Division of Nephrology, Department of Medicine, and Department of Physiology, The Johns Hopkins University School of Medicine, 21205, Baltimore, Maryland

    Suresh V. Ambudkar

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  1. Gregory L. Evans
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Evans, G.L., Ni, B., Hrycyna, C.A. et al. Heterologous expression systems for P-glycoprotein:E. coli, yeast, and baculovirus. J Bioenerg Biomembr 27, 43–52 (1995). https://doi.org/10.1007/BF02110330

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  • DOI: https://doi.org/10.1007/BF02110330

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