The dysfunction of the E3 ubiquitin ligase Parkin is a key contributor to the development of early-onset Parkinson's disease. Parkin is responsible for the labelling of outer mitochondrial membrane proteins with the small modifier protein ubiquitin in response to oxidative stress. This ubiquitylation signals the clearance of the damaged mitochondria to preserve overall cell health. Recent structural and biochemical experiments have shown that native Parkin exists in an autoinhibited state that must be activated in order to unmask its full ubiquitylation potential. In a recent article in the Biochemical Journal (vol. 460, pp. 127–139), Kazlauskaite and co-workers identified that the Parkinson's disease-associated kinase PINK1 [PTEN (phosphatase and tensin homologue deleted on chromosome 10)-induced putative kinase 1] can phosphorylate ubiquitin in response to mitochondrial depolarization. Furthermore, the authors demonstrated that phosphorylated ubiquitin can activate Parkin's E3 ligase activity and promote both increased autoubiquitylation and substrate ubiquitylation of the mitochondrial protein Miro1. The study provides exciting initial insights that show how PINK1 might activate ubiquitin through phosphorylation, and how this important regulatory step might switch on Parkin-mediated ubiquitylation.
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June 2014
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Commentary|
May 29 2014
Switching on ubiquitylation by phosphorylating a ubiquitous activator
Gary S. Shaw
Gary S. Shaw
1
*Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1
1email gshaw1@uwo.ca
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Publisher: Portland Press Ltd
Received:
April 08 2014
Accepted:
April 09 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 460 (3): e1–e3.
Article history
Received:
April 08 2014
Accepted:
April 09 2014
Connected Content
This is a commentary on:
Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65
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Citation
Gary S. Shaw; Switching on ubiquitylation by phosphorylating a ubiquitous activator. Biochem J 15 June 2014; 460 (3): e1–e3. doi: https://doi.org/10.1042/BJ20140459
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