Inhibition of N-linked glycosylation of P-glycoprotein by tunicamycin results in a reduced multidrug resistance phenotype

R. Kramer, T. K. Weber, R. Arceci, N. Ramchurren, W. V. Kastrinakis, G. Steele, I. C. Summerhayes

Research output: Contribution to journalArticle

Abstract

Characterisation of altered glycosylation of P-glycoprotein (P-gp) found associated with the absence of a multidrug resistance (MDR) phenotype in cell lines prompted an investigation to assess the role of post-translational processing in establishing P-gp efflux pump functionality. The clone A cell line used in this study displays a strong MDR phenotype mediated by high constitutive levels of expression of P-gp. Incubation of clone A cells with tunicamycin for different periods resulted in a time-dependent increase in daunorubicin accumulation, reflecting a reduction in P-gp function. Parallel experiments conducted with verapamil resulted in no loss of P-gp functionality in clone A cells. Reduction in surface-associated P-gp following exposure to tunicamycin was established by FACS analysis, Western blot analysis and immunoprecipitation of surface-iodinated P-gp. In addition, immunoprecipitation of P-gp from 32p-orthophosphate-labelled cells demonstrated reduced phosphorylation of P-gp associated with tunicamycin exposure. From these studies we conclude that glycosylation of P-gp is required to establish the cellular MDR phenotype.

Original languageEnglish (US)
Pages (from-to)670-675
Number of pages6
JournalBritish journal of cancer
Volume71
Issue number4
DOIs
StatePublished - Apr 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kramer, R., Weber, T. K., Arceci, R., Ramchurren, N., Kastrinakis, W. V., Steele, G., & Summerhayes, I. C. (1995). Inhibition of N-linked glycosylation of P-glycoprotein by tunicamycin results in a reduced multidrug resistance phenotype. British journal of cancer, 71(4), 670-675. https://doi.org/10.1038/bjc.1995.133