| First Author | Van Humbeeck C | Year | 2008 |
| Journal | Eur J Neurosci | Volume | 27 |
| Issue | 2 | Pages | 284-93 |
| PubMed ID | 18190519 | Mgi Jnum | J:132191 |
| Mgi Id | MGI:3775364 | Doi | 10.1111/j.1460-9568.2007.06000.x |
| Citation | Van Humbeeck C, et al. (2008) Parkin occurs in a stable, non-covalent, approximately 110-kDa complex in brain. Eur J Neurosci 27(2):284-93 |
| abstractText | Mutations in the gene for parkin, a 52-kDa E3 ubiquitin ligase, are a major cause of hereditary Parkinson's disease (PD). In vitro studies have identified a large number of parkin-interacting proteins. Whether parkin exists as a monomer or as part of a stable protein complex in vivo is uncertain. Here we demonstrate that endogenous parkin occurs in a stable, non-covalent, approximately 110-kDa complex in native extracts from mouse brain, heart and skeletal muscle, while monomeric parkin is undetectable. Partial denaturation experiments indicate that this complex is at least a tetramer. Reported parkin-binding partners do not show detectable association with the parkin complex on native gels. Upon overexpression in COS1, SH-SY5Y or CHO cells, parkin accumulates predominantly as a monomer, suggesting that the interactors required for complex formation are available in limiting amounts in these cells. Importantly, PD-linked parkin mutations significantly impair parkin complex formation. These data demonstrate that parkin oligomerizes into a stable, non-covalent, heteromeric complex in vivo, and suggest that parkin may have as yet unidentified stable binding partners. |
