| First Author | Clements CM | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 41 | Pages | 15091-6 |
| PubMed ID | 17015834 | Mgi Jnum | J:169897 |
| Mgi Id | MGI:4943400 | Doi | 10.1073/pnas.0607260103 |
| Citation | Clements CM, et al. (2006) DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc Natl Acad Sci U S A 103(41):15091-6 |
| abstractText | DJ-1/PARK7, a cancer- and Parkinson's disease (PD)-associated protein, protects cells from toxic stresses. However, the functional basis of this protection has remained elusive. We found that loss of DJ-1 leads to deficits in NQO1 [NAD(P)H quinone oxidoreductase 1], a detoxification enzyme. This deficit is attributed to a loss of Nrf2 (nuclear factor erythroid 2-related factor), a master regulator of antioxidant transcriptional responses. DJ-1 stabilizes Nrf2 by preventing association with its inhibitor protein, Keap1, and Nrf2's subsequent ubiquitination. Without intact DJ-1, Nrf2 protein is unstable, and transcriptional responses are thereby decreased both basally and after induction. This effect of DJ-1 on Nrf2 is present in both transformed lines and primary cells across human and mouse species. DJ-1's effect on Nrf2 and subsequent effects on antioxidant responses may explain how DJ-1 affects the etiology of both cancer and PD, which are seemingly disparate disorders. Furthermore, this DJ-1/Nrf2 functional axis presents a therapeutic target in cancer treatment and justifies DJ-1 as a tumor biomarker. |
