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

58 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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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