relation between ubiquitin system and parkinsonism

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Parkin belongs to a family of proteins with conserved UBL and RING finger motifs. Mutations in parkin cause the autosomal recessive juvenile form of parkinsonism (AR-JP). In the patients with parkin mutations, there is selective loss of dopaminergic neurons without the presence of Lewy bodies. Before this research, we showed that parkin had an ubiquitin protein-ligase activity. According to this, we began to identify the substrate and regulator of parkin. To this end, we performed yeast two-hybrid screening using parkin as a bait, purification of parkin binding proteins. Until now, we isolated some candidate of parkin substrate, and examining their reliability using C. elegans, which possesses possible parkin gene. We already isolated two allele of parkin mutant. Now we are analyzing the phenotype caused by disruption of parkin gene, although the parkin gene seems to be non-essential for the viability.