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- Publisher Website: 10.1073/pnas.0607260103
- Scopus: eid_2-s2.0-33750052885
- PMID: 17015834
- WOS: WOS:000241247300021
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Article: DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2
Title | DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2 |
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Authors | |
Keywords | NQO1 Keap1 Neurodegeneration PARK7 Oxidative stress |
Issue Date | 2006 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2006, v. 103, n. 41, p. 15091-15096 How to Cite? |
Abstract | 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. © 2006 by The National Academy of Sciences of the USA. |
Persistent Identifier | http://hdl.handle.net/10722/291764 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Clements, Casey M. | - |
dc.contributor.author | McNally, Richard S. | - |
dc.contributor.author | Conti, Brian J. | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Ting, Jenny P.Y. | - |
dc.date.accessioned | 2020-11-17T14:55:04Z | - |
dc.date.available | 2020-11-17T14:55:04Z | - |
dc.date.issued | 2006 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2006, v. 103, n. 41, p. 15091-15096 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291764 | - |
dc.description.abstract | 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. © 2006 by The National Academy of Sciences of the USA. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | NQO1 | - |
dc.subject | Keap1 | - |
dc.subject | Neurodegeneration | - |
dc.subject | PARK7 | - |
dc.subject | Oxidative stress | - |
dc.title | DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2 | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.0607260103 | - |
dc.identifier.pmid | 17015834 | - |
dc.identifier.pmcid | PMC1586179 | - |
dc.identifier.scopus | eid_2-s2.0-33750052885 | - |
dc.identifier.volume | 103 | - |
dc.identifier.issue | 41 | - |
dc.identifier.spage | 15091 | - |
dc.identifier.epage | 15096 | - |
dc.identifier.isi | WOS:000241247300021 | - |
dc.identifier.issnl | 0027-8424 | - |