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Neddylation positively regulates the ubiquitin E3 ligase activity of parkin
Author(s) -
Um Ji Won,
Han Kyung Ah,
Im Eunju,
Oh Yohan,
Lee Kyule,
Chung Kwang Chul
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22828
Subject(s) - parkin , neddylation , nedd8 , ubiquitin ligase , ubiquitin , proteasome , microbiology and biotechnology , drosophila melanogaster , biology , parkinson's disease , chemistry , genetics , biochemistry , gene , disease , medicine
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. © 2012 Wiley Periodicals, Inc.