Functional expression of human P-glycoprotein in Schizosaccharomyces pombe.
Human MDR1 cDNA was introduced into the human cultured cells KB-3-1 and Schizosaccharomyces pombe pmd1 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.
Ueda
K
K
Department of Agricultural Chemistry, Kyoto University, Japan.
Shimabuku
A M
AM
Konishi
H
H
Fujii
Y
Y
Takebe
S
S
Nishi
K
K
Yoshida
M
M
Beppu
T
T
Komano
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000255:Adenosine Triphosphate / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D006096:Gramicidin / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D008562:Membrane Glycoproteins / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D012568:Schizosaccharomyces / Q000235:genetics*; D014634:Valinomycin / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D006096:Gramicidin; D003609:Dactinomycin; D014634:Valinomycin; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D004247:DNA