Reference Report
| Reference | |||
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| Citation | Meulener, M.C., Xu, K., Thomson, L., Ischiropoulos, H., Bonini, N.M. (2006). Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging. Proc. Natl. Acad. Sci. U.S.A. 103(33): 12517--12522. (Export to RIS) | ||
| FlyBase ID | FBrf0193931 | ||
| Publication Type | Research paper | ||
| PubMed ID | 16894167 | ||
| PubMed Abstract | Inherited mutations in PARK7, the gene encoding DJ-1, are associated with loss of protein function and early-onset parkinsonism. Like human DJ-1 (hDJ-1), Drosophila DJ-1b protects against oxidative insult and is modified with oxidation. We demonstrate that hDJ-1 rescues flies mutant for DJ-1b, and that a conserved cysteine residue in the fly protein (C104, analogous to C106 in hDJ-1) is critical for biological antioxidant function in vivo. Targeted mutagenesis suggests that modification of DJ-1b at this residue inactivates the protective activity of the protein against oxidative stress. Further studies show that DJ-1 modification increases dramatically with age in flies, mice, and humans, with aged flies showing strikingly increased susceptibility to oxidative stress and markedly enhanced DJ-1b modification upon oxidative challenge. Overoxidation of DJ-1 with age and exposure to oxidative toxins may lead to inactivation of DJ-1 function, suggesting a role in susceptibility to sporadic Parkinson's disease. | ||
| DOI | 10.1073/pnas.0601891103 | ||
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| Language of Publication | English | ||
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| Publication Type | Journal | ||
| Abbreviation | Proc. Natl. Acad. Sci. U.S.A. | ||
| Title | Proceedings of the National Academy of Sciences of the United States of America | ||
| Publication Year | 1915- | ||
| ISBN/ISSN | 0027-8424 | ||
Data from Reference
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Alleles (11)
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Constructs (8)
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Genes (5)
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Natural transposons (1)
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