Parkin degrades estrogen-related receptors to limit the expression of monoamine oxidases.
Parkin, whose mutations cause Parkinson disease (PD), controls oxidative stress by limiting the expression of monoamine oxidases (MAO)--mitochondrial enzymes responsible for the oxidative de-amination of dopamine. Here, we show that parkin performed this function by increasing the ubiquitination and degradation of estrogen-related receptors (ERR), orphan nuclear receptors that play critical ... roles in the transcription regulation of many nuclear-encoded mitochondrial proteins. All three ERRs (α, β and γ) increased the transcription of MAOs A and B; the effects were abolished by parkin, but not by its PD-linked mutants. Parkin bound to ERRs and increased their ubiquitination and degradation. In fibroblasts from PD patients with parkin mutations or brain slices from parkin knockout mice, degradation of ERRs was significantly attenuated. The results reveal the molecular mechanism by which parkin suppresses the transcription of MAOs to control oxidative stress induced by dopamine oxidation.
Mesh Terms:
Animals, Cell Line, Gene Expression Regulation, Enzymologic, Humans, Mice, Mice, Knockout, Monoamine Oxidase, Oxidative Stress, Parkinson Disease, Promoter Regions, Genetic, Protein Binding, Receptors, Estrogen, Ubiquitin-Protein Ligases, Ubiquitination
Animals, Cell Line, Gene Expression Regulation, Enzymologic, Humans, Mice, Mice, Knockout, Monoamine Oxidase, Oxidative Stress, Parkinson Disease, Promoter Regions, Genetic, Protein Binding, Receptors, Estrogen, Ubiquitin-Protein Ligases, Ubiquitination
Hum. Mol. Genet.
Date: Mar. 15, 2011
PubMed ID: 21177257
View in: Pubmed Google Scholar
Download Curated Data For This Publication
124022
Switch View:
- Interactions 4
- PTM Genes 3