NR AQMK
AU Mange,A.; Crozet,C.A.; Lehmann,S.; Beranger,F.
TI Scrapie-like prion protein is translocated to the nuclei of infected cells independently of proteasome inhibition and interacts with chromatin
QU Journal of Cell Science 2004 May 1; 117(11): 2411-6
PT journal article
AB Prion diseases are fatal transmissible neurodegenerative disorders characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrPc) denoted PrPsc. 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
MH Active Transport, Cell Nucleus; Animals; Cell Line, Tumor; Cell Nucleus/*metabolism; Chromatin/*metabolism; DNA/metabolism; Endopeptidase K/metabolism; Mice; Microtubules/metabolism; Neuroblastoma/*metabolism/virology; PrPsc Proteins/genetics/*metabolism; Proteasome Endopeptidase Complex/*antagonists & inhibitors/metabolism; Protein Binding; Research Support, Non-U.S. Gov't; Scrapie/metabolism
AD Institut de Genetique Humaine, UPR CNRS1142, 141 Rue de la Cardonille 34396 Montpellier CEDEX 5, France.
SP englisch
PO England