The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity
Open accessAbstract
Mutation in leucine-rich repeat kinase-2 ( LRRK2 ) is the most common cause of late-onset Parkinson's disease (PD). Although most cases of PD are sporadic, some are inherited, including those caused by LRRK2 mutations. Because these mutations may be associated with a toxic gain of function, controlling the expression of LRRK2 may decrease its cytotoxicity. Here we show that the carboxyl terminus of HSP70-interacting protein (CHIP) binds, ubiquitinates, and promotes the ubiquitin proteasomal degradation of LRRK2. Overexpression of CHIP protects against and knockdown of CHIP exacerbates toxicity mediated by mutant LRRK2. Moreover, HSP90 forms a complex with LRRK2, and inhibition of HSP90 chaperone activity by 17AAG leads to proteasomal degradation of LRRK2, resulting in increased cell viability. Thus, increasing CHIP E3 ligase activity and blocking HSP90 chaperone activity can prevent the deleterious effects of LRRK2. These findings point to potential treatment options for LRRK2-associated PD.
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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
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481
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Self-citationKinase activity of mutant LRRK2 mediates neuronal toxicity
Smith, W. W., Pei, Z., Jiang, H., Dawson, V. L., Dawson, T. M., & Ross, C. A. (2006) · Nature Neuroscience · doi:10.1038/nn1776 · Cited by 619
Self-citation
Cited by
Interplay of LRRK2 with chaperone-mediated autophagy
Orenstein, S. J., Kuo, S.-H., Tasset, I., Arias, E., Koga, H., Fernandez-Carasa, I., Cortes, E., Honig, L. S., Dauer, W., Consiglio, A., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3350 · Cited by 588
Beilina, A., Rudenko, I. N., Kaganovich, A., Civiero, L., Chau, H., Kalia, S. K., Kalia, L. V., Lobbestael, E., Chia, R., Ndukwe, K., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318306111 · Cited by 348
Jackson, S. E. (2012) · Topics in Current Chemistry · doi:10.1007/128_2012_356 · Cited by 338
SQSTM1/p62: a potential target for neurodegenerative disease
Ma, S., Attarwala, I. Y., & Xie, X.-Q. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00516 · Cited by 185
Mechanisms of protein toxicity in neurodegenerative diseases
Chung, C. G., Lee, H., & Lee, S. B. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2854-4 · Cited by 142
Metadata
- Authors
- Ko, H. S., Bailey, R., Smith, W. W., Liu, Z., Shin, J.-H., Lee, Y.-I., Zhang, Y.-J., Jiang, H., Ross, C. A., Moore, D. J., Patterson, C., Petrucelli, L., Dawson, T. M., & Dawson, V. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-02-24
- Volume
- 106
- Issue
- 8
- Pages
- 2897-2902
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1969362677
- Cited by
- 208
- References
- 5
- FWCI
- 15.94
- Type
- journal article
- Language
- en
- Open access
- green
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- Ko, H. S., Bailey, R., Smith, W. W., Liu, Z., Shin, J.-H., Lee, Y.-I., Zhang, Y.-J., Jiang, H., Ross, C. A., Moore, D. J., Patterson, C., Petrucelli, L., Dawson, T. M., & Dawson, V. L. (2009). CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0810123106
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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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