N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 H2O 2, 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.

Original languageEnglish (US)
Article numbere99654
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 24 2014

Fingerprint

Ubiquitin Thiolesterase
Parkinson disease
ubiquitin
hydrolases
Parkinson Disease
Carbonyl Cyanide m-Chlorophenyl Hydrazone
Rotenone
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Deuterium
rotenone
Dopaminergic Neurons
Flexible structures
Post Translational Protein Processing
deuterium
Tandem Mass Spectrometry
post-translational modification
Neuroblastoma
mice
Cell death
Disulfides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kim, H. J., Kim, H. J., Jeong, J. E., Baek, J. Y., Jeong, J., Kim, S., ... Lee, K. J. (2014). N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage. PLoS One, 9(6), [e99654]. https://doi.org/10.1371/journal.pone.0099654

N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage. / Kim, Hee Jung; Kim, Hyun Jung; Jeong, Jae Eun; Baek, Jeong Yeob; Jeong, Jaeho; Kim, Sun; Kim, Young-Mee; Kim, Youhwa; Nam, Jin Han; Huh, Sue Hee; Seo, Jawon; Jin, Byung Kwan; Lee, Kong Joo.

In: PLoS One, Vol. 9, No. 6, e99654, 24.06.2014.

Research output: Contribution to journalArticle

Kim, HJ, Kim, HJ, Jeong, JE, Baek, JY, Jeong, J, Kim, S, Kim, Y-M, Kim, Y, Nam, JH, Huh, SH, Seo, J, Jin, BK & Lee, KJ 2014, 'N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage', PLoS One, vol. 9, no. 6, e99654. https://doi.org/10.1371/journal.pone.0099654
Kim HJ, Kim HJ, Jeong JE, Baek JY, Jeong J, Kim S et al. N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage. PLoS One. 2014 Jun 24;9(6). e99654. https://doi.org/10.1371/journal.pone.0099654
Kim, Hee Jung ; Kim, Hyun Jung ; Jeong, Jae Eun ; Baek, Jeong Yeob ; Jeong, Jaeho ; Kim, Sun ; Kim, Young-Mee ; Kim, Youhwa ; Nam, Jin Han ; Huh, Sue Hee ; Seo, Jawon ; Jin, Byung Kwan ; Lee, Kong Joo. / N-terminal truncated UCH-L1 prevents Parkinson's disease associated damage. In: PLoS One. 2014 ; Vol. 9, No. 6.
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