title: Scrapie-like prion protein is translocated to the nuclei of infected cells independently of proteasome inhibition and interacts with chromatin.
abstract: 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
authors.affiliation: Institut de Génétique Humaine, UPR CNRS1142, 141 Rue de la Cardonille 34396 Montpellier CEDEX 5, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Mangé
authors.forename: Carole
authors.initials: C
authors.lastname: Crozet
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
authors.forename: Florence
authors.initials: F
authors.lastname: Béranger
mesh_terms: 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
chemical_list: D002843:Chromatin; D018620:PrPSc Proteins; D061988:Proteasome Inhibitors; D004247:DNA; D019286:Endopeptidase K; D046988:Proteasome Endopeptidase Complex