Functional expression of human P‐glycoprotein in Schizosaccharomyces pombe

Abstract
Human MDR1 cDNA was introduced into the human cultured cells KB‐3‐1 and Schizosaccharomyces pombe pmdI null mutant KN3. The drug sensitivity of KB‐G2 and KN3/pgp, expressing human P‐glycoprotein, was examined. KB‐G2 was resistant to the peptide antibiotics valinomycin and gramicidin D as well as having a typical multidrug resistance (MDR) phenotype. KN3/pgp was resistant to valinomycin and actinomycin D, but not to adriamycin. The ATP‐hydrolysis‐deficient mutant did not confer KN3 resistance to these antibiotics. Human P‐glycoprotein expressed in S. pombe seemed to lack N‐glycosylation. The N‐glycosylation‐deficient mutant, however, conferred a typical MDR phenotype on KB‐3‐1. These results suggest that human P‐glycoprotein functions as an efflux pump of valinomycin and actinomycin D in the membrane of S. pombe.

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