Mutations in the parkin gene are a common cause of autosomal recessive early-onset parkinsonism. Parkin functions as an E3 ubiquitin ligase where it can polyubiquitinate a number of its protein substrates, thus targeting them for degradation by the 26 S proteasomal complex. Recent studies have demonstrated that alternative modes of parkin-mediated ubiquitination may serve other non-degradative regulatory roles. In addition, parkin appears to function as a multipurpose neuroprotectant in a number of toxic paradigms. Coupled with these observations, parkin may integrate other gene products associated with parkinsonism, including α-synuclein, LRRK2 (leucine-rich repeat kinase 2), DJ-1 and PINK1 [PTEN (phosphatase and tensin homologue deleted on chromosome 10)-induced putative kinase 1], into a common biochemical pathway of potential relevance to disease pathogenesis. Parkin therefore represents a unique multifaceted ubiquitin ligase consistent with an important housekeeping role in maintaining the integrity or survival of dopaminergic neurons.
Skip Nav Destination
Conference Article| October 25 2006
Parkin: a multifaceted ubiquitin ligase
D.J. Moore 1
1Institute for Cell Engineering and Department of Neurology, Johns Hopkins University School of Medicine, 733 North Broadway, Broadway Research Building, Suite 731, Baltimore, MD 21205, U.S.A.
Search for other works by this author on:
- Views Icon Views
- Share Icon Share
D.J. Moore; Parkin: a multifaceted ubiquitin ligase. Biochem Soc Trans 1 October 2006; 34 (5): 749–753. doi: https://doi.org/10.1042/BST0340749
Download citation file:
Don't already have an account? Register
Get Access To This Article
Buy This Article