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Biochem Soc Trans. 2006 Nov;34(Pt 5):749-53.

Parkin: a multifaceted ubiquitin ligase.

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1
Institute for Cell Engineering and Department of Neurology, Johns Hopkins University School of Medicine, 733 North Broadway, Broadway Research Building, Suite 731, Baltimore, MD 21205, USA. dmoore20@jhmi.edu

Abstract

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 alpha-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.

PMID:
17052189
DOI:
10.1042/BST0340749
[Indexed for MEDLINE]
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