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Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN
| 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 | | oncogene | | PTEN | | oxidative stress | | transformation |
| 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 |
| URI: | http://hdl.handle.net/2115/44305 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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