Prolyl isomerase Pin1 regulates doxorubicin-inducible P-glycoprotein level by reducing Foxo3 stability

Taiki Shimizu, Yoshimasa Bamba, Yosuke Kawabe, Tomokazu Fukuda, Fumihiro Fujimori, Katsuhiko Takahashi, Chiyoko Uchida, Takafumi Uchida

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

It has been known that the phosphoSer/Thr-Pro-specific peptidyl prolyl cis/trans isomerase Pin1 regulates a variety of intracellular signaling pathways, including the response to the genotoxic drug doxorubicin. Pin1 binds phosphorylated p53 and stabilizes p53 to cause cell cycle arrest and apoptosis quickly in response to doxorubicin. Here we show another mechanism of Pin1 to maintain cell sensitivity to genotoxic stress, irrespective of whether p53 is present or not. In response to the genotoxic drug, Pin1 binds and decreases levels of the phosphorylated Foxo3, the positive transcription factor of P-glycoprotein (P-gp) gene. Through this mechanism of action, Pin1 decreases the level of P-gp and signals the cell to pump the genotoxic drugs out. This shows that Pin1 is implemented in maintaining the susceptibility to the genotoxic drugs by controlling P-gp level as well as p53-dependent apoptosis and cell cycle signaling pathways.

Original languageEnglish
Pages (from-to)328-333
Number of pages6
JournalBiochemical and biophysical research communications
Volume471
Issue number2
DOIs
Publication statusPublished - 2016 Mar 4

Keywords

  • Doxorubicin
  • Foxo3
  • P-glycoprotein
  • Pin1
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Shimizu, T., Bamba, Y., Kawabe, Y., Fukuda, T., Fujimori, F., Takahashi, K., Uchida, C., & Uchida, T. (2016). Prolyl isomerase Pin1 regulates doxorubicin-inducible P-glycoprotein level by reducing Foxo3 stability. Biochemical and biophysical research communications, 471(2), 328-333. https://doi.org/10.1016/j.bbrc.2016.02.014