The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Ubiquitylation of synphilin-1 and α-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease
Open accessAbstract
Parkinson's disease (PD) is a neurodegenerative disease characterized by Lewy body formation and death of dopaminergic neurons. Mutations in α-synuclein and parkin cause familial forms of PD. Synphilin-1 was shown to interact with α-synuclein and to promote the formation of cytosolic inclusions. We now report that synphilin-1 interacts with the E3 ubiquitin-ligases SIAH-1 and SIAH-2. SIAH proteins ubiquitylate synphilin-1 both in vitro and in vivo , promoting its degradation by the ubiquitin–proteasome system. Inability of the proteasome to degrade synphilin-1/SIAH complex leads to a robust formation of ubiquitylated cytosolic inclusions. Ubiquitylation is required for inclusion formation, because a catalytically inactive mutant of SIAH-1, which still binds to synphilin-1, fails to promote inclusions. Like synphilin-1, α-synuclein associates with SIAH in intact cells, but the interaction with SIAH-2 was much stronger that with SIAH-1. In vitro experiments show that SIAH-2 monoubiquitylates α-synuclein. Further evidence that SIAH proteins may play a role in inclusion formation comes from the demonstration of SIAH immunoreactivity in Lewy bodies of PD patients.
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Self-citationProteasomal function is impaired in substantia nigra in Parkinson’s disease
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A binding motif for Siah ubiquitin ligase
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Cited by
Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies
Ciechanover, A., & Kwon, Y. T. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.117 · Cited by 898
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Cell Biology and Pathophysiology of α-Synuclein
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Metadata
- Authors
- Liani, E., Eyal, A., Avraham, E., Shemer, R., Szargel, R., Berg, D., Bornemann, A., Riess, O., Ross, C. A., Rott, R., & Engelender, S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-04-02
- Volume
- 101
- Issue
- 15
- Pages
- 5500-5505
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1998180291
- Cited by
- 193
- References
- 10
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- green
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- Liani, E., Eyal, A., Avraham, E., Shemer, R., Szargel, R., Berg, D., Bornemann, A., Riess, O., Ross, C. A., Rott, R., & Engelender, S. (2004). Ubiquitylation of synphilin-1 and α-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0401081101
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