Functionally active homodimer of P-glycoprotein in multidrug-resistant tumor cells.
P-glycoprotein plays a key role in multidrug resistance of tumor cells. In order to elucidate the possible quarternary structure/function relationship of P-glycoprotein, we treated multidrug-resistant human leukemia K562/ADM cells with the crosslinking reagent, disuccinimidyl suberate. In addition to 180K P-glycoprotein, a 340K protein was immunoprecipitated with an anti-P-glycoprotein monoclonal antibody, MRK-16. The 340K protein is most probably a dimeric P-glycoprotein, since only the 180K P-glycoprotein was immunoprecipitated with MRK-16 when K562/ADM cells were treated with the cleavable crosslinking reagent, dithiobis(succinimidylpropionate), and analysed under reduced conditions. The dimeric P-glycoprotein was photolabeled with [3H]azidopine like the 180K monomeric P-glycoprotein and the photolabeling was inhibited by excess amount of vincristine and verapamil. The dimeric P-glycoprotein could be a functionally active form of the protein involved in the transport of antitumor agents.
Institute of Applied Microbiology, University of Tokyo, Japan.
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Naito
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Tsuruo
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001386:Azides / Q000378:metabolism; D004095:Dihydropyridines / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008936:Mitolactol / Q000494:pharmacology; D008937:Mitomycins / Q000494:pharmacology; D011233:Precipitin Tests; D013388:Succinimides; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001386:Azides; D004095:Dihydropyridines; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008937:Mitomycins; D013388:Succinimides; D014750:Vincristine; C041130:azidopine; D004317:Doxorubicin; D014700:Verapamil; D008936:Mitolactol; C019358:disuccinimidyl suberate