The UCH-L1 gene encodes two opposing enzymatic activities that affect α-synuclein degradation and Parkinson's disease susceptibility

Yichin Liu, Lara Fallon, Hilal A. Lashuel, Zhihua Liu, Peter T. Lansbury

Research output: Contribution to journalArticle

616 Citations (Scopus)

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 α-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.

Original languageEnglish
Pages (from-to)209-218
Number of pages10
JournalCell
Volume111
Issue number2
DOIs
Publication statusPublished - 18 Oct 2002
Externally publishedYes

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Ubiquitin Thiolesterase
Synucleins
Disease Susceptibility
Parkinson Disease
Genes
Hydrolases
Degradation
Ligases
Enzymes
Dimerization
Proteolysis
Cultured Cells
Cells
Health

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

The UCH-L1 gene encodes two opposing enzymatic activities that affect α-synuclein degradation and Parkinson's disease susceptibility. / Liu, Yichin; Fallon, Lara; Lashuel, Hilal A.; Liu, Zhihua; Lansbury, Peter T.

In: Cell, Vol. 111, No. 2, 18.10.2002, p. 209-218.

Research output: Contribution to journalArticle

Liu, Yichin ; Fallon, Lara ; Lashuel, Hilal A. ; Liu, Zhihua ; Lansbury, Peter T. / The UCH-L1 gene encodes two opposing enzymatic activities that affect α-synuclein degradation and Parkinson's disease susceptibility. In: Cell. 2002 ; Vol. 111, No. 2. pp. 209-218.
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