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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this