Scrapie-like prion protein is translocated to the nuclei of infected cells independently of proteasome inhibition and interacts with chromatin.
Prion diseases are fatal transmissible neurodegenerative disorders characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrP(C)) denoted PrP(Sc). Recently, wild-type and pathogenic PrP mutants have been shown to be degraded by the endoplasmic reticulum-associated degradation proteasome pathway after translocation into the cytosol. We show here that a protease resistant form of PrP accumulated in the nuclei of prion-infected cells independently of proteasome activity, and that this nuclear translocation required an intact microtubule network. Moreover, our results show for the first time that nuclear PrP interacts with chromatin in vivo, which may have physiopathological consequences in prion diseases
Mangé
Alain
A
Institut de Génétique Humaine, UPR CNRS1142, 141 Rue de la Cardonille 34396 Montpellier CEDEX 5, France.
Crozet
Carole
C
Lehmann
Sylvain
S
Béranger
Florence
F
D021581:Active Transport, Cell Nucleus; D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D019286:Endopeptidase K / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000821:virology; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding; D012608:Scrapie / Q000378:metabolism
D002843:Chromatin; D018620:PrPSc Proteins; D061988:Proteasome Inhibitors; D004247:DNA; D019286:Endopeptidase K; D046988:Proteasome Endopeptidase Complex