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

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Title: Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN
Authors: Kim, Yun-Chul Browse this author
Kitaura, Hirotake Browse this author
Taira, Takahiro Browse this author
Iguchi-Ariga, Sanae M. M. Browse this author
Ariga, Hiroyoshi Browse this author →KAKEN DB
Keywords: DJ-1
oxidative stress
Issue Date: Dec-2009
Publisher: Spandidos Publications
Journal Title: International Journal of Oncology
Volume: 35
Issue: 6
Start Page: 1331
End Page: 1341
Publisher DOI: 10.3892/ijo_00000451
Abstract: 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.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 有賀 寛芳

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