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Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs
Author(s) -
Mima Shinji,
Ushijima Hironori,
Hwang Hyun-Jung,
Tsutsumi Shinji,
Makise Masaki,
Yamaguchi Yoshihiro,
Tsuchiya Tomofusa,
Mizushima Hiroshi,
Mizushima Tohru
Publication year - 2007
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/j.febslet.2007.03.001
Subject(s) - major facilitator superfamily , efflux , gene , yeast , transporter , saccharomyces cerevisiae , multiple drug resistance , biology , drug resistance , microbiology and biotechnology , biochemistry
Non‐steroidal anti‐inflammatory drugs (NSAIDs), such as indomethacin, have serious gastrointestinal side effects. Since their direct cytotoxicity was suggested to be involved in this side effect, we here tried to identify NSAID‐resistant genes. We screened for Saccharomyces cerevisiae genes whose overexpression causes indomethacin resistance and identified the TPO1 gene, which encodes a major facilitator superfamily transporter. Its overexpression or deletion made yeast cells resistant or sensitive, respectively, to some NSAIDs. A BLAST search identified the possible human orthologue of Tpo1p, tetracycline transporter‐like protein (TETRAN), whose overexpression in cultured human cells caused resistance to some NSAIDs, suggesting that TETRAN is an efflux pump for some NSAIDs.