Linked Life Data

21743439

Source:http://linkedlifedata.com/resource/pubmed/id/21743439

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2011-8-3
pubmed:abstractText
Prion diseases are associated with the conversion of cellular prion protein (PrP(C)) to toxic ?-sheet isoforms (PrP(Sc)), which are reported to inhibit the ubiquitin-proteasome system (UPS). Accordingly, UPS substrates accumulate in prion-infected mouse brains, suggesting impairment of the 26S proteasome. A direct interaction between its 20S core particle and PrP isoforms was demonstrated by immunoprecipitation. ?-PrP aggregates associated with the 20S particle, but did not impede binding of the PA26 complex, suggesting that the aggregates do not bind to its ends. Aggregated ?-PrP reduced the 20S proteasome's basal peptidase activity, and the enhanced activity induced by C-terminal peptides from the 19S ATPases or by the 19S regulator itself, including when stimulated by polyubiquitin conjugates. However, the 20S proteasome was not inhibited when the gate in the ?-ring was open due to a truncation mutation or by association with PA26/PA28. These PrP aggregates inhibit by stabilising the closed conformation of the substrate entry channel. A similar inhibition of substrate entry into the proteasome may occur in other neurodegenerative diseases where misfolded ?-sheet-rich proteins accumulate.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1460-2075
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3065-77
pubmed:dateRevised
2011-10-7
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Misfolded PrP impairs the UPS by interaction with the 20S proteasome and inhibition of substrate entry.
pubmed:affiliation
Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural