Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs

Shinji Mima, Hironori Ushijima, Hyun Jung Hwang, Shinji Tsutsumi, Masaki Makise, Yoshihiro Yamaguchi, Tomofusa Tsuchiya, Hiroshi Mizushima, Tohru Mizushima

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18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1457-1463
Number of pages7
JournalFEBS Letters
Volume581
Issue number7
DOIs
Publication statusPublished - 2007 Apr 3

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Keywords

  • Non-steroidal anti-inflammatory drugs
  • TPO1
  • Tetracycline transporter-like protein

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Mima, S., Ushijima, H., Hwang, H. J., Tsutsumi, S., Makise, M., Yamaguchi, Y., Tsuchiya, T., Mizushima, H., & Mizushima, T. (2007). Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs. FEBS Letters, 581(7), 1457-1463. https://doi.org/10.1016/j.febslet.2007.03.001