Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65
University of Dundee · MRC Protein Phosphorylation and Ubiquitylation Unit · +1 more institution
Abstract
We have previously reported that the Parkinson's disease-associated kinase PINK1 (PTEN-induced putative kinase 1) is activated by mitochondrial depolarization and stimulates the Parkin E3 ligase by phosphorylating Ser65 within its Ubl (ubiquitin-like) domain. Using phosphoproteomic analysis, we identified a novel ubiquitin phosphopeptide phosphorylated at Ser65 that was enriched 14-fold in HEK (human embryonic kidney)-293 cells overexpressing wild-type PINK1 stimulated with the mitochondrial uncoupling agent CCCP (carbonyl cyanide m-chlorophenylhydrazone), to activate PINK1, compared with cells expressing kinase-inactive PINK1. Ser65 in ubiquitin lies in a similar motif to Ser65 in the Ubl domain of Parkin.…
Citation impact
- FWCI
- 36.42
- Percentile
- 100%
- References
- 43
Authors
10- AKAgne KazlauskaiteCorresponding
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
- CKChandana Kondapalli
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
- RGRobert Gourlay
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
- DGDavid G. Campbell
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
- MSMaria Stella Ritorto
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
Topics & keywords
- Parkin
- PINK1
- Ubiquitin ligase
- Phosphorylation
- Chemistry
- Ubiquitin
- Kinase
- Molecular biology