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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ahmad, S., Safa, A. R., and Glazer, R.I. (1994).Biochemistry 33, 10313–10318.
Alnemri, E. S., Fernandes-Alnemri, T., Nelki, D. S., Dudley, K., Dubois, G. C., and Litwack, G. (1993).Proc. Natl. Acad. Sci. USA 90, 6839–6843.
Al-Shawi, M. K., and Senior, A. E. (1993).J. Biol. Chem 268, 4197–4206.
Ambudkar, S. V., Lelong, I. H., Zhang, J., Cardarelli, C. O., Gottesman, M. M., and Pastan, I. (1992).Proc. Natl. Acad. Sci. USA 89, 8472–8476.
Balzi, E., and Goffeau, A. (1991).Biochim. Biophys. Acta 1073, 241–252.
Baubichon-Cortay, H., Baggetto, L. G., Dayan, G., and Di Pietro, A. (1994).J. Biol. Chem. 269, 22983–22989.
Barnes, H. J., Arlotto, M. P., and Waterman, M. R. (1991).Proc. Natl. Acad. Sci. USA 88, 5597–5601.
Bear, C. E., Li, C., Kartner, N., Bridges, R. J., Jensen, T. J., Ramjeesingh, M., and Riordan, J. R. (1992).Cell 68, 809–818.
Bibi, E., and Béjá, O. (1994).J. Biol. Chem. 269, 19910–19915.
Bibi, E., Gros, P., and Kaback, H. R. (1993).Proc. Natl. Acad. Sci. USA 90, 9209–9213.
Bruggemann, E. P., Germann, U. A., Gottesman, M. M., and Pastan, I. (1989).J. Biol. Chem. 264. 15483–15488.
Bruggemann, E. P., Chaudhary, V., Gottesman, M. M., and Pastan, I. (1991).Biotechniques 10, 202–209.
Bruggemann, E. P., Currier, S. J., Gottesman, M. M., and Pastan, I. (1992).J. Biol. Chem. 267, 21020–21026.
Chen, C.-J., Chin, C. E., Ueda, K., Clark, D. P., Pastan, I., Gottesmann, M. M., and Roninson, I. B. (1986).Cell 47, 381–389.
Choi, K., Chen, C.-J., Kriegler, M., and Roninson, I. B. (1988).Cell 53, 519–529.
Currier, S. J., Kane, S. E., Willingham, M. C., Cardarelli, C. O., Pastan, I., and Gottesman, M. M. (1992).J. Biol. Chem. 267, 25153–25159.
Currier, S. J., Ueda, K., Willingham, M. C., Pastan, I., and Gottesman, M. M. (1989).J. Biol. Chem. 264, 14376–14381.
Devine, S. E., Ling, V., and Melera, P. W. (1992).Proc. Natl. Acad. Sci. USA 89, 4564–4568.
Ferreira, G. C., and Pedersen, P. L. (1992).J. Biol. Chem. 267, 5460–5466.
Fiermonte, G., Walker, J. E., and Palmieri, F. (1993).Biochem. J. 294, 293–299.
Germann, U. A., Willingham, M. C., Pastan, I., and Gottesman, M. M. (1990).Biochemistry 29, 2295–2303.
Germann, U. A., Pastan, I., and Gottesman, M. M. (1993).Sem. Cell Biol. 4, 63–76.
Gill, D. R., Hyde, S. C., Higgins, C. F., Valverde, M. A., Mintenig, G. M., and SepÚlveda, F. V. (1992).Cell 71, 23–32.
Gottesmann, M. M., and Pastan, I. (1988).J. Biol. Chem. 263, 12163–12166.
Gottesman, M. M., and Pastan, I. (1993)Annu. Rev. Biochem. 62, 385–427.
Greenberger, L. (1993).J. Biol. Chem. 268, 11417–11425.
Gros, P., Croop, J., and Housman, D. (1986).Cell 47, 371–380.
Gros, P., Dhir, R., Croop, J., and Talbot, F. (1991).Proc. Natl. Acad. Sci. USA 88, 7289–7293.
Gros, P., Talbot, F., Tang-Wei, D., Bibi, E., and Kaback, H. R. (1992).Biochemistry 31, 1992–1998.
Higgins, C. F. (1992).Annu. Rev. Cell Biol. 8, 67–113.
Janknecht, R., de Martynoff, G., Lou, J., Hipskind, R.A., Nordheim, A., and Stunnenberg, H.G. (1991).Proc. Natl. Acad. Sci USA 88, 8972–8976.
Juliano, R. L., and Ling, V. (1976).Biochim. Biophys. Acta 455, 152–162.
Kartner, N., Hanrahan, J. W., Jensen, T. J., Naismith, L., Sun, S., Ackerley, C. A., Reyes, E. F., Tsui, L.-C., Rommens, J. M., Bear, C. E., and Riordan, J. R. (1991).Cell 64, 681–691.
Kitts, P. A., and Possee, R. D. (1993).Biotechniques 14, 810–817.
Kuchler, K., and Thorner, J. (1992).Proc. Natl. Acad. Sci. USA 89, 2302–2306.
Kuchler, K., Goransson, H. M., Viswanathan, M. N., and Thorner, J. (1992).Cold Spring Harbor Symp. Quant. Biol. 57, 579–592.
Li, C., Ramjeesingh, M., Reyes, E., Jensen, T., Chang, X., Rommens, J. M., and Bear, C. E. (1993).Nature Genetics 3, 311–316.
Loo, T. W., and Clarke, D. M. (1993a).J. Biol. Chem. 268, 3143–3149.
Loo, T. W., and Clarke, D. M. (1993b).J. Biol. Chem. 268, 19965–19972.
Loo, T. W., and Clarke, D. M. (1994a).J. Biol. Chem. 269, 7243–7248.
Loo, T. W., and Clarke, D. M. (1994b).J. Biol. Chem. 269, 7750–7755.
Morris, D. I., Greenberger, L. M., Bruggemann, E. P., Cardarelli, C., Gottesman, M. M., Pastan, I., and Seamon, K. (1994).Mol. Pharmacol. 46, 329–337.
Nakamoto, R. K., Rao, R., and Slayman, C. W. (1991)J. Biol. Chem. 266, 7940–7949.
Rao, U. S., and Scarborough, G. A. (1994).Mol. Pharmacol. 45, 773–776.
Rao, U. S., Fine, R. L., and Scarborough, G. A. (1994a).Biochem. Pharmacol. 48, 287–292.
Rao, V. V., Chiu, M. L., Kronauge, J. F., and Piwnica-Worms, D. (1994b).J. Nucl. Med. 35, 500–515.
Raymond, M., Gros, P., Whiteway, M., and Thomas, D. Y. (1992).Science 256, 232–233.
Raymond, M., Ruetz, S., Thomas, D. Y., and Gros, P. (1994).Mol. Cell. Biol. 14, 277–286.
Reddy, P., Peterkofsky, A., and McKenney, K. (1989).Nucleic Acids Res. 17, 10473–10488.
Richert, N. D., Aldwin, L., Nitecki, D., Gottesman, M. M., and Pastan, I. (1988).Biochemistry 27, 7607–7613.
Ruetz, S., and Gros, P. (1994a).J. Biol. Chem. 269, 12277–12284.
Ruetz, S., and Gros, P. (1994b).Cell 77, 1071–1081.
Ruetz, S., Raymond, M., and Gros, P. (1993).Proc. Natl. Acad. Sci. USA 90, 11588–11592.
Saeki, T., Shimabuku, A. M., Azuma, Y., Shibano, Y., Komano, T., and Ueda, K. (1991).Agric. Biol. Chem. 55, 1859–1865.
Saeki, T., Ueda, K., Tanigawara, Y., Hori, R., and Komano, T. (1993).J. Biol. Chem. 268, 6077–6080.
Sarkadi, B., Price, E. M., Boucher, R. C., Germann, U. A., and Scarborough, G. (1992).J. Biol. Chem. 267, 4854–4858.
Sarkadi, B., Muller, M., Homolya, L., Hollo, Z., Seprodi, J., Germann, U. A., Gottesman, M. M., Price, E. M., and Boucher, R. C. (1994).FASEB J. 8, 766–770.
Sarkar, H. K., Thorens, B., Lodish, H. F., and Kaback, H. R. (1988).Proc. Natl. Acad. Sci. USA 85, 5463–5467.
Schinkel, A. H., Kemp, S., Dolle, M., Rudenko, G., and Wagenaar, Els (1993).J. Biol. Chem. 268, 7474–7481.
Skach, W. R., and Lingappa, V. R. (1994).Cancer Res. 54, 3202–3209.
Strosberg, A.D. (1992).Mol. Neurobiol. 4, 211–250.
Tanaka, S., Currier, S. J., Bruggemann, E. P., Ueda, K., Germann, U. A., Pastan, I., and Gottesman, M. M. (1990).Biochem. Biophys. Res. Commun. 166, 180–186.
Yoshimura, A., Kuwazura, Y., Sumizawa, T., Ichikawa, M., Ikeda, S., Ueda, T., and Akiyama, S.-I. (1989).J. Biol. Chem. 264, 16282–16291.
Valverde, M. A., Diáz, M., SepÚlveda, F. V., Gill, D. R., Hyde, S. C., and Higgins, C. F. (1992).Nature (London) 355, 830–833.
Zhang, L., Sachs, C. W., Fine, R. L., and Casey, P. (1994).J. Biol. Chem. 269, 15973–15976.
Zhang, J.-T, Duthie, M., and Ling, V. (1993).J. Biol. Chem. 268, 15101–15110.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02110330