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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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

Fingerprint

Ubiquitin-Protein Ligases
Parkinsonian Disorders
Ubiquitin
Ubiquitin-Conjugating Enzymes
Proteasome Endopeptidase Complex
Parkinson Disease
Cell Death
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Um, Ji Won ; Han, Kyung Ah ; Im, Eunju ; Oh, Yohan ; Lee, Kyule ; Chung, Kwang Chul. / Neddylation positively regulates the ubiquitin E3 ligase activity of parkin. In: Journal of Neuroscience Research. 2012 ; Vol. 90, No. 5. pp. 1030-1042.
@article{ed3918281094467d85ff87fe12cfdaca,
title = "Neddylation positively regulates the ubiquitin E3 ligase activity of parkin",
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.",
author = "Um, {Ji Won} and Han, {Kyung Ah} and Eunju Im and Yohan Oh and Kyule Lee and Chung, {Kwang Chul}",
year = "2012",
month = "5",
day = "1",
doi = "10.1002/jnr.22828",
language = "English",
volume = "90",
pages = "1030--1042",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "5",

}

Neddylation positively regulates the ubiquitin E3 ligase activity of parkin. / Um, Ji Won; Han, Kyung Ah; Im, Eunju; Oh, Yohan; Lee, Kyule; Chung, Kwang Chul.

In: Journal of Neuroscience Research, Vol. 90, No. 5, 01.05.2012, p. 1030-1042.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neddylation positively regulates the ubiquitin E3 ligase activity of parkin

AU - Um, Ji Won

AU - Han, Kyung Ah

AU - Im, Eunju

AU - Oh, Yohan

AU - Lee, Kyule

AU - Chung, Kwang Chul

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84862829058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862829058&partnerID=8YFLogxK

U2 - 10.1002/jnr.22828

DO - 10.1002/jnr.22828

M3 - Article

C2 - 22271254

AN - SCOPUS:84862829058

VL - 90

SP - 1030

EP - 1042

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 5

ER -