Abstract |
Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been proposed as one of the Parkinson's disease (PD) related genes, but the possible molecular connection between UCH-L1 and PD is not well understood. In this study, we discovered an N-terminal 11 amino acid truncated variant UCH-L1 that we called NT-UCH-L1, in mouse brain tissue as well as in NCI-H157 lung cancer and SH-SY5Y neuroblastoma cell lines. In vivo experiments and hydrogen- deuterium exchange (HDX) with tandem mass spectrometry (MS) studies showed that NT-UCH-L1 is readily aggregated and degraded, and has more flexible structure than UCH-L1. Post-translational modifications including monoubiquitination and disulfide crosslinking regulate the stability and cellular localization of NT-UCH-L1, as confirmed by mutational and proteomic studies. Stable expression of NT-UCH-L1 decreases cellular ROS levels and protects cells from H2O2, rotenone and CCCP-induced cell death. NT-UCH-L1-expressing transgenic mice are less susceptible to degeneration of nigrostriatal dopaminergic neurons seen in the MPTP mouse model of PD, in comparison to control animals. These results suggest that NT-UCH-L1 may have the potential to prevent neural damage in diseases like PD.
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Authors | Hee-Jung Kim, Hyun Jung Kim, Jae-Eun Jeong, Jeong Yeob Baek, Jaeho Jeong, Sun Kim, Young-Mee Kim, Youhwa Kim, Jin Han Nam, Sue Hee Huh, Jawon Seo, Byung Kwan Jin, Kong-Joo Lee |
Journal | PloS one
(PLoS One)
Vol. 9
Issue 6
Pg. e99654
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24959670
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ubiquitin carboxyl-Terminal Hydrolase L-1, human
- Hydrogen Peroxide
- Ubiquitin Thiolesterase
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Topics |
- Animals
- Brain
(enzymology, pathology)
- Cell Line, Tumor
- Deuterium Exchange Measurement
- Disease Models, Animal
- Enzyme Stability
- HeLa Cells
- Humans
- Hydrogen Peroxide
(pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Mitochondria
(metabolism)
- Parkinson Disease
(genetics, pathology)
- Protein Processing, Post-Translational
- Ubiquitin Thiolesterase
(chemistry, genetics, metabolism)
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