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Molecules 2017, 22(7), 1104; doi:10.3390/molecules22071104

L1210 Cells Overexpressing ABCB1 Drug Transporters Are Resistant to Inhibitors of the N- and O-glycosylation of Proteins

1
Institute of Molecular Physiology and Genetics, Centre of Bioscience, Slovak Academy of Sciences, Dúbravska cesta 9, 84005 Bratislava, Slovakia
2
Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia
*
Authors to whom correspondence should be addressed.
Received: 1 June 2017 / Revised: 27 June 2017 / Accepted: 28 June 2017 / Published: 3 July 2017
(This article belongs to the Special Issue Protein-Carbohydrate Interactions)
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Abstract

Overexpression of P-glycoprotein (P-gp, drug transporter) in neoplastic cells is the most frequently observed molecular cause of multidrug resistance. Here, we show that the overexpression of P-gp in L1210 cells leads to resistance to tunicamycin and benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside (GalNAc-α-O-benzyl). Tunicamycin induces both glycosylation depression and ubiquitination improvement of P-gp. However, the latter is not associated with large increases in molecular mass as evidence for polyubiquitination. Therefore, P-gp continues in maturation to an active membrane efflux pump rather than proteasomal degradation. P-gp-positive L1210 cells contain a higher quantity of ubiquitin associated with cell surface proteins than their P-gp-negative counterparts. Thus, P-gp-positive cells use ubiquitin signaling for correct protein folding to a higher extent than P-gp-negative cells. Elevation of protein ubiquitination after tunicamycin treatment in these cells leads to protein folding rather than protein degradation, resulting at least in the partial lack of cell sensitivity to tunicamycin in L1210 cells after P-gp expression. In contrast to tunicamycin, to understand why P-gp-positive cells are resistant to GalNAc-α-O-benzyl, further research is needed. View Full-Text
Keywords: L1210 cells; P-glycoprotein; multidrug resistance; N-glycosylation; O-glycosylation; tunicamycin; benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside; ubiquitination L1210 cells; P-glycoprotein; multidrug resistance; N-glycosylation; O-glycosylation; tunicamycin; benzyl 2-acetamido-2-deoxy-α-d-galactopyranoside; ubiquitination
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Pavlikova, L.; Seres, M.; Hano, M.; Bohacova, V.; Sevcikova, I.; Kyca, T.; Breier, A.; Sulova, Z. L1210 Cells Overexpressing ABCB1 Drug Transporters Are Resistant to Inhibitors of the N- and O-glycosylation of Proteins. Molecules 2017, 22, 1104.

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