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

Yuzuru Imai, Mariko Soda, Tetsuro Murakami, Mikio Shoji, Koji Abe, Ryosuke Takahashi

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)51901-51910
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number51
DOIs
Publication statusPublished - Dec 19 2003

Fingerprint

Lewy Bodies
Cell death
Cell Death
Genes
Molecular Chaperones
Parkinson Disease
Chaperonins
HSP90 Heat-Shock Proteins
HSP70 Heat-Shock Proteins
Dopaminergic Neurons
Parkinsonian Disorders
Human Genome
Proteasome Endopeptidase Complex
Ligases
Ubiquitin
Proteolysis
Neurons
Degradation
Molecules
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

A Product of the Human Gene Adjacent to parkin Is a Component of Lewy Bodies and Suppresses Pael Receptor-induced Cell Death. / Imai, Yuzuru; Soda, Mariko; Murakami, Tetsuro; Shoji, Mikio; Abe, Koji; Takahashi, Ryosuke.

In: Journal of Biological Chemistry, Vol. 278, No. 51, 19.12.2003, p. 51901-51910.

Research output: Contribution to journalArticle

Imai, Yuzuru ; Soda, Mariko ; Murakami, Tetsuro ; Shoji, Mikio ; Abe, Koji ; Takahashi, Ryosuke. / A Product of the Human Gene Adjacent to parkin Is a Component of Lewy Bodies and Suppresses Pael Receptor-induced Cell Death. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 51. pp. 51901-51910.
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