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DOI: 10.1016/b978-012078185-0/50622-3
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  • Biology

Abstract

Publisher Summary The MDR1 gene contains 28 introns, of which 26 interrupt the protein coding sequence. The P-glycoprotein (P-gp) product of the MDR1 gene is expressed in the small intestine, colon, kidney, liver, and adrenal, with very low levels of expression in most other tissues. Normal peripheral blood and bone marrow cells express very low amounts of P-gp, but it is expressed in practically all hamatopoietic progenitor cells with the highest levels in pluripotent stem cells. MDR1 belongs to the ABC superfamily of ATP-binding transport proteins that includes the product of the cystic fibrosis gene (CFTR), the Plasmodium falciparum multidrug resistance protein (pfMDR), and a large number of bacterial periplasmic transport proteins. P-gp has been shown to utilize ATP to pump hydrophobic drugs out of cells, thus decreasing their intracellular concentration and hence their toxicity. The MDR1 gene is amplified in multidrug-resistant cell lines. However the actual physiological role of P-gp is not clear, although recent evidence suggests two possibilities that are not mutually exclusive.

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