The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
L166P Mutant DJ-1, Causative for Recessive Parkinson's Disease, Is Degraded through the Ubiquitin-Proteasome System
Open accessAbstract
Mutations in a gene on chromosome 1, DJ-1, have been reported recently to be associated with recessive, earlyonset Parkinson's disease. While one mutation is a large deletion that is predicted to produce an effective knockout of the gene, the second is a point mutation, L166P, whose precise effects on protein function are unclear. In the present study, we show that L166P destabilizes DJ-1 protein and promotes its degradation through the ubiquitin-proteasome system. A double mutant (K130R, L166P) was more stable than L166P, suggesting that this lysine residue contributes to stability of the protein. Subcellular localization was broadly similar for both wild type and L166P forms of the protein, indicating that the effect of the mutation is predominantly on protein stability. These observations are reminiscent of other recessive gene mutations that produce an effective loss of function. The L166P mutation has the simple effect of promoting DJ-1 degradation, thereby reducing net DJ-1 protein within the cell.
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Cites
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Shimura, H., Hattori, N., Kubo, S.-I., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., et al. (2000) · Nature Genetics · doi:10.1038/77060 · Cited by 2,024
Zhang, Y., Gao, J., Chung, K. K. K., Huang, H., Dawson, V. L., & Dawson, T. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.240347797 · Cited by 982
Cited by
Canet-Avilés, R. M., Wilson, M. A., Miller, D. W., Ahmad, R., McLendon, C., Bandyopadhyay, S., Baptista, M. J., Ringe, D., Petsko, G. A., & Cookson, M. R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402959101 · Cited by 1,116
Self-citationThe Ubiquitin Proteasome System in Neurodegenerative Diseases
Ciechanover, A., & Brundin, P. (2003) · Neuron · doi:10.1016/s0896-6273(03)00606-8 · Cited by 982
Expanding insights of mitochondrial dysfunction in Parkinson's disease
Abou-Sleiman, P. M., Muqit, M. M. K., & Wood, N. W. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1868 · Cited by 869
DJ‐1 has a role in antioxidative stress to prevent cell death
Taira, T., Saito, Y., Niki, T., Iguchi‐Ariga, S. M. M., Takahashi, K., & Ariga, H. (2004) · EMBO reports · doi:10.1038/sj.embor.7400074 · Cited by 853
Mitochondrial dysfunction in Parkinson's disease
Winklhofer, K. F., & Haass, C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.08.013 · Cited by 688
Metadata
- Authors
- Miller, D. W., Ahmad, R., Hague, S., Baptista, M. J., Canet-Aviles, R., McLendon, C., Carter, D. M., Zhu, P.-P., Stadler, J., Chandran, J., Klinefelter, G. R., Blackstone, C., & Cookson, M. R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 278
- Issue
- 38
- Pages
- 36588-36595
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2103551853
- Cited by
- 236
- References
- 4
- FWCI
- 15.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Miller, D. W., Ahmad, R., Hague, S., Baptista, M. J., Canet-Aviles, R., McLendon, C., Carter, D. M., Zhu, P.-P., Stadler, J., Chandran, J., Klinefelter, G. R., Blackstone, C., & Cookson, M. R. (2003). L166P Mutant DJ-1, Causative for Recessive Parkinson's Disease, Is Degraded through the Ubiquitin-Proteasome System. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m304272200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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