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Publication : A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death.

First Author  Imai Y Year  2003
Journal  J Biol Chem Volume  278
Issue  51 Pages  51901-10
PubMed ID  14532270 Mgi Jnum  J:213906
Mgi Id  MGI:5586802 Doi  10.1074/jbc.M309655200
Citation  Imai Y, et al. (2003) A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death. J Biol Chem 278(51):51901-10
abstractText  Parkin, a RING-type ubiquitin ligase, is the product of the gene responsible for autosomal recessive juvenile parkinsonism. A reverse strand gene located upstream of the parkin gene in the human genome has been identified. The gene product, termed Glup/PACRG, forms a large molecular chaperone complex containing heat shock proteins 70 and 90 and chaperonin components. Glup suppressed cell death induced by accumulation of unfolded Pael receptor (Pael-R), a substrate of Parkin. On the other hand, Glup facilitated the formation of inclusions consisting of Pael-R, molecular chaperones, protein degradation molecules, and Glup itself, when proteasome is inhibited. Glup knockdown attenuated the formation of Pael-R inclusions, which resulted in the promotion of cell death with extensive vacuolization. Moreover, Glup turned out to be a component of Lewy bodies in Parkinson's disease cases. These data suggest that Glup may play an important role in the formation of Lewy bodies and protection of dopaminergic neurons against Parkinson's disease.
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