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Overexpression of LaMDR2, a novel multidrug resistance ATP‐binding cassette transporter, causes 5‐fluorouracil resistance in Leishmania amazonensis 1
Author(s) -
Katakura Ken,
Fujise Hiroshi,
Takeda Keiichi,
Kaneko Osamu,
Torii Motomi,
Suzuki Mamoru,
Chang Kwang Poo,
Hashiguchi Yoshihisa
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00130-9
Subject(s) - atp binding cassette transporter , leishmania , multiple drug resistance , biology , subfamily , transporter , kinetoplastida , drug resistance , multidrug resistance associated proteins , microbiology and biotechnology , biochemistry , gene , parasite hosting , immunology , protozoal disease , world wide web , computer science , malaria
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.