Overexpression of LaMDR2, a novel multidrug resistance ATP-binding cassette transporter, causes 5-fluorouracil resistance in Leishmania amazonensis.
The ATP-binding cassette (ABC) proteins play an important role in drug resistance and detoxification in various organisms. Here we isolated LaMDR2, a new member of the multidrug resistance (MDR) subfamily of ABC proteins in Leishmania amazonensis. LaMDR2 exhibited 47% amino acid identity to its most closely related protein, LaMDR1, which was previously isolated from the same species. Promastigotes that overexpressed LaMDR2 showed significant resistance to 5-fluorouracil (5-FU), but not to LaMDR1 substrates. Expression of LaMDR2 in the transfectants was relatively higher in the log phase than the stationary phase, and a lower accumulation of [(3)H]5-FU was observed in the log-phase cells. These results suggest that LaMDR2 is involved in extrusion of xenobiotics, but functionally different from LaMDR1.
Katakura
Ken
K
Department of Parasitology, Gunma University Graduate School of Medical Science, Maebashi, Gunma 371-8511, Japan. kenkata@med.gunma-u.ac.jp
Fujise
Hiroshi
H
Takeda
Keiichi
K
Kaneko
Osamu
O
Torii
Motomi
M
Suzuki
Mamoru
M
Chang
Kwang Poo
KP
Hashiguchi
Yoshihisa
Y
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D004351:Drug Resistance; D005472:Fluorouracil / Q000494:pharmacology*; D007891:Leishmania / Q000737:chemistry* / Q000502:physiology; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000302:isolation & purification / Q000502:physiology; D016415:Sequence Alignment; D017385:Sequence Homology; D013379:Substrate Specificity; D014162:Transfection
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D015800:Protozoan Proteins; C095122:multidrug resistance protein 3; D005472:Fluorouracil