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

Kim, Yun-Chul

Kitaura, Hirotake

Taira, Takahiro

Iguchi-Ariga, Sanae M. M.

Ariga, Hiroyoshi

  • Other DJ-1
  • Other oncogene
  • Other PTEN
  • Other oxidative stress
  • Other transformation
  • NDC 491
  • DJ-1 is all 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-I 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.
PublisherSpandidos Publications
Date Issued 2009-12
NIItypejournal article
Identifier URI
  • isIdenticalTo DOI
    • ISSN 1019-6439
    • International Journal of Oncology
    35(6), 1331-1341