The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome

Taocong Jin, Yaping Gu, Gianluigi Zanusso, Man Sun Sy, Anil Kumar, Mark Cohen, Pierluigi Gambetti, Neena Singh

Research output: Contribution to journalArticlepeer-review

145 Scopus citations


Familial prion diseases are thought to result from a change in structure of the mutant prion protein (PrP), which takes a pathogenic conformation. We have examined the role of molecular chaperones in the folding of normal and mutant PrP Q217R (PrP217) in transfected neuroblastoma cells. In a previous report we showed that, although most of the PrP217 forms escape the endoplasmic reticulum quality control system and aggregate in post-Golgi compartments, a significant proportion of PrP217 retains the C-terminal glycosylphosphatidyl inositol signal peptide (PrP32), and does not exit the endoplasmic reticulum (Singh, N., Zanusso, G., Chen, S. G., Fujioka, H., Richardson, S., Gambetti, P., and Petersen, R. B. (1997) J. Biol. Chem. 272, 28461-28470). We have now studied the folding and turnover of PrP32 to understand the mechanism by which abnormal PrP forms cause cellular toxicity in our cell culture model and in the human brain carrying the Gerstmann-Straussler-Scheinker disease Q217R mutation. In this report, we show that PrP32 remains associated with the chaperone BiP for an abnormally prolonged period of time and is degraded by the proteasomal pathway. This study is the first demonstration that BiP is chaperoning the folding of PrP and plays a role in maintaining the quality control in the PrP maturation pathway. Our data provide new insight into the diverse pathways of mutant PrP metabolism and neurotoxicity.

Original languageEnglish (US)
Pages (from-to)38699-38704
Number of pages6
JournalJournal of Biological Chemistry
Issue number49
StatePublished - Dec 8 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome'. Together they form a unique fingerprint.

Cite this