A Product of the Human Gene Adjacent to parkin Is a Component of Lewy Bodies and Suppresses Pael Receptor-induced Cell Death

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 comple...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-12, Vol.278 (51), p.51901-51910
Main Authors: Imai, Yuzuru, Soda, Mariko, Murakami, Tetsuro, Shoji, Mikio, Abe, Koji, Takahashi, Ryosuke
Format: Article
Language:English
Subjects:
Base Sequence
Cell Death
Cell Line
Cysteine Endopeptidases
HSP70 Heat-Shock Proteins
hsp90 protein
Humans
Inclusion Bodies
Lewy Bodies - chemistry
Microfilament Proteins
Molecular Chaperones
Molecular Sequence Data
Multienzyme Complexes
Neurons - pathology
Neurons - ultrastructure
PACRG protein
Pael protein
Parkin protein
Proteasome Endopeptidase Complex
Proteins - metabolism
Proteins - physiology
Receptors, G-Protein-Coupled - physiology
Transfection
Ubiquitin-Protein Ligases - metabolism
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M309655200