Neddylation positively regulates the ubiquitin E3 ligase activity of parkin

Ji Won Um, Kyung Ah Han, Eunju Im, Yohan Oh, Kyule Lee, Kwang Chul Chung

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Abstract

Mutations in the parkin gene underlie a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinsonism (AR-JP). Dysfunction of parkin, a ubiquitin E3 ligase, has been implicated in the accumulation of ubiquitin proteasome system-destined substrates and eventually leads to cell death. However, regulation of parkin enzymatic activity is incompletely understood. Here we investigated whether the ubiquitin E3 ligase activity of parkin could be regulated by neddylation. We found that parkin could be a target of covalent modification with NEDD8, a ubiquitin-like posttranslational modifier. In addition, NEDD8 attachment caused an increase of parkin activity through the increased binding affinity for ubiquitin-conjugating E2 enzyme as well as the enhanced formation of the complex containing parkin and substrates. These findings point to the functional importance of NEDD8 and suggest that neddylation is one to the diverse modes of parkin regulation, potentially linking it to the pathogenesis of AR-JP.

Original languageEnglish
Pages (from-to)1030-1042
Number of pages13
JournalJournal of Neuroscience Research
Volume90
Issue number5
DOIs
Publication statusPublished - 2012 May 1

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All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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