Activation mechanisms of the E3 ubiquitin ligase parkin

Nikhil Panicker, Valina Dawson, Ted M Dawson

Research output: Contribution to journalReview article

Abstract

Monogenetic, familial forms of Parkinson's disease (PD) only account for 5-10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin, encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated. Its dysfunction underlies both inherited and idiopathic PD-associated neurodegeneration. Here, we review recent literature that provides a model of activation of parkin in the setting of mitochondrial damage that involves PINK1 (PTEN-induced kinase-1) and phosphoubiquitin. We note that neuronal parkin is primarily a cytosolic protein (with various non-mitochondrial functions), and discuss potential cytosolic parkin activation mechanisms.

Original languageEnglish (US)
Pages (from-to)3075-3086
Number of pages12
JournalBiochemical Journal
Volume474
Issue number18
DOIs
StatePublished - Sep 15 2017

Fingerprint

Ubiquitin-Protein Ligases
Parkinson Disease
Chemical activation
Genes
Phosphotransferases
Amino Acids
Substrates
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Activation mechanisms of the E3 ubiquitin ligase parkin. / Panicker, Nikhil; Dawson, Valina; Dawson, Ted M.

In: Biochemical Journal, Vol. 474, No. 18, 15.09.2017, p. 3075-3086.

Research output: Contribution to journalReview article

@article{c88038df96f64bcbbf9ddd3b721ae78d,
title = "Activation mechanisms of the E3 ubiquitin ligase parkin",
abstract = "Monogenetic, familial forms of Parkinson's disease (PD) only account for 5-10{\%} of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin, encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated. Its dysfunction underlies both inherited and idiopathic PD-associated neurodegeneration. Here, we review recent literature that provides a model of activation of parkin in the setting of mitochondrial damage that involves PINK1 (PTEN-induced kinase-1) and phosphoubiquitin. We note that neuronal parkin is primarily a cytosolic protein (with various non-mitochondrial functions), and discuss potential cytosolic parkin activation mechanisms.",
author = "Nikhil Panicker and Valina Dawson and Dawson, {Ted M}",
year = "2017",
month = "9",
day = "15",
doi = "10.1042/BCJ20170476",
language = "English (US)",
volume = "474",
pages = "3075--3086",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "18",

}

TY - JOUR

T1 - Activation mechanisms of the E3 ubiquitin ligase parkin

AU - Panicker, Nikhil

AU - Dawson, Valina

AU - Dawson, Ted M

PY - 2017/9/15

Y1 - 2017/9/15

N2 - Monogenetic, familial forms of Parkinson's disease (PD) only account for 5-10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin, encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated. Its dysfunction underlies both inherited and idiopathic PD-associated neurodegeneration. Here, we review recent literature that provides a model of activation of parkin in the setting of mitochondrial damage that involves PINK1 (PTEN-induced kinase-1) and phosphoubiquitin. We note that neuronal parkin is primarily a cytosolic protein (with various non-mitochondrial functions), and discuss potential cytosolic parkin activation mechanisms.

AB - Monogenetic, familial forms of Parkinson's disease (PD) only account for 5-10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin, encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated. Its dysfunction underlies both inherited and idiopathic PD-associated neurodegeneration. Here, we review recent literature that provides a model of activation of parkin in the setting of mitochondrial damage that involves PINK1 (PTEN-induced kinase-1) and phosphoubiquitin. We note that neuronal parkin is primarily a cytosolic protein (with various non-mitochondrial functions), and discuss potential cytosolic parkin activation mechanisms.

UR - http://www.scopus.com/inward/record.url?scp=85029386536&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029386536&partnerID=8YFLogxK

U2 - 10.1042/BCJ20170476

DO - 10.1042/BCJ20170476

M3 - Review article

C2 - 28860335

AN - SCOPUS:85029386536

VL - 474

SP - 3075

EP - 3086

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 18

ER -