Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN

  • Authors:
    • Yun-Chul Kim
    • Hirotake Kitaura
    • Takahiro Taira
    • Sanae M.M. Iguchi-Ariga
    • Hiroyoshi Ariga
  • View Affiliations

  • Published online on: December 1, 2009     https://doi.org/10.3892/ijo_00000451
  • Pages: 1331-1341
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Abstract

DJ-1 is an oncogene and also a causative gene for a familial form of Parkinson's disease. DJ-1 has multiple functions, including anti-oxidative stress reaction and cysteine 106 (C106) of DJ-1 is an essential amino acid for DJ-1 to exert its function. While increased expression and secretion of DJ-1 into serum in patients with various cancers and regulation of p53 and PTEN by DJ-1 have been reported, the molecular mechanism underlying oncogenicity of DJ-1 is poorly understood. Here, we analyzed the function of DJ-1 in the PI3'K signaling pathway under an oxidative stress condition, focusing on the interaction of DJ-1 with PTEN. We found that both wild-type (wt) and C106S-DJ-1, a substitution mutant of DJ-1, directly bound to PTEN and inhibited PTEN phosphatase activity but that C106S-DJ-1 more strongly inhibited the activity than did wt-DJ-1. When NIH3T3 cells were treated with H2O2, oxidation of C106 of wt-DJ-1 occurred, accompanied by increased binding of wt-DJ-1 to PTEN, decreased PTEN activity and increased phosphorylation of AKT. C106S-DJ-1 transformed cells more strongly than did wt-DJ-1 and the transforming activity of DJ-1 was enhanced by H2O2 treatment of cells in which increased binding of DJ-1 to PTEN and decreased PTEN activity were observed. Furthermore, TOF-MS analysis of the oxidative status of C106 suggested that DJ-1 activity requires the presence of the reduced form of C106, which accounts for >50% of the total form. These results suggest that the oxidative status of DJ-1 regulates PTEN activity, leading to cell proliferation and transformation.

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December 2009
Volume 35 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Kim, Y., Kitaura, H., Taira, T., Iguchi-Ariga, S.M., & Ariga, H. (2009). Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN. International Journal of Oncology, 35, 1331-1341. https://doi.org/10.3892/ijo_00000451
MLA
Kim, Y., Kitaura, H., Taira, T., Iguchi-Ariga, S. M., Ariga, H."Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN". International Journal of Oncology 35.6 (2009): 1331-1341.
Chicago
Kim, Y., Kitaura, H., Taira, T., Iguchi-Ariga, S. M., Ariga, H."Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN". International Journal of Oncology 35, no. 6 (2009): 1331-1341. https://doi.org/10.3892/ijo_00000451