Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
Zur Ablage hinzufügen
  Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben
Zeitschriftenartikel

Association of Bcl-2 with misfolded prion protein is linked to the toxic potential of cytosolic PrP

MPG-Autoren
/persons/resource/persons241710

Rambold,  Angelika
Department of Developmental Immunobiology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Externe Ressourcen

https://www.molbiolcell.org/doi/10.1091/mbc.e06-01-0083
(Verlagsversion)

Volltexte (beschränkter Zugriff)
Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.
Volltexte (frei zugänglich)

Rambold et al. 2006.pdf
(Verlagsversion), 2MB

Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Rambold, A., Miesbauer, M., Rapaport, D., Bartke, T., Baier, M., Winklhofer, K. F., et al. (2006). Association of Bcl-2 with misfolded prion protein is linked to the toxic potential of cytosolic PrP. Molecular and Cellular Biology (Washington, DC), 17, 3356-3368. doi:10.1091/mbc.e06-01-0083.


Zitierlink: https://hdl.handle.net/21.11116/0000-0007-8BB8-D
Zusammenfassung
Protein misfolding is linked to different neurodegenerative disorders like Alzheimer’s disease, polyglutamine, and prion diseases. We investigated the cytotoxic effects of aberrant conformers of the prion protein (PrP) and show that toxicity is specifically linked to misfolding of PrP in the cytosolic compartment and involves binding of PrP to the anti-apoptotic protein Bcl-2. PrP targeted to different cellular compartments, including the cytosol, nucleus, and mitochondria, adopted a misfolded and partially proteinase K–resistant conformation. However, only in the cytosol did the accumulation of misfolded PrP induce apoptosis. Apoptotic cell death was also induced by two pathogenic mutants of PrP, which are partially localized in the cytosol. A mechanistic analysis revealed that the toxic potential is linked to an internal domain of PrP (amino acids 115–156) and involves coaggregation of cytosolic PrP with Bcl-2. Increased expression of the chaperones Hsp70 and Hsp40 prevented the formation of PrP/Bcl-2 coaggregates and interfered with PrP-induced apoptosis. Our study reveals a compartment-specific toxicity of PrP misfolding that involves coaggregation of Bcl-2 and indicates a protective role of molecular chaperones.