Abstract |
The assumption that each enzyme expresses a single enzymatic activity in vivo is challenged by the linkage of the neuronal enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1) to Parkinson's disease (PD). UCH-L1, especially those variants linked to higher susceptibility to PD, causes the accumulation of alpha-synuclein in cultured cells, an effect that cannot be explained by its recognized hydrolase activity. UCH-L1 is shown here to exhibit a second, dimerization-dependent, ubiquityl ligase activity. A polymorphic variant of UCH-L1 that is associated with decreased PD risk (S18Y) has reduced ligase activity but comparable hydrolase activity as the wild-type enzyme. Thus, the ligase activity as well as the hydrolase activity of UCH-L1 may play a role in proteasomal protein degradation, a critical process for neuronal health.
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Authors | Yichin Liu, Lara Fallon, Hilal A Lashuel, Zhihua Liu, Peter T Lansbury Jr |
Journal | Cell
(Cell)
Vol. 111
Issue 2
Pg. 209-18
(Oct 18 2002)
ISSN: 0092-8674 [Print] United States |
PMID | 12408865
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Nerve Tissue Proteins
- SNCA protein, human
- Snca protein, rat
- Synucleins
- alpha-Synuclein
- Thiolester Hydrolases
- Ubiquitin Thiolesterase
- Ligases
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Topics |
- Animals
- Brain Chemistry
- COS Cells
- Dimerization
- Gene Dosage
- Genetic Predisposition to Disease
- Humans
- Ligases
(metabolism)
- Models, Molecular
- Mutation
- Nerve Tissue Proteins
(metabolism)
- Parkinson Disease
(genetics)
- Polymorphism, Genetic
- Rabbits
- Rats
- Synaptic Vesicles
(chemistry)
- Synucleins
- Thiolester Hydrolases
(analysis, genetics)
- Transfection
- Ubiquitin Thiolesterase
- alpha-Synuclein
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