Document Detail


α-Secretase-Derived Cleavage of Cellular Prion Yields Biologically Active Catabolites with Distinct Functions.
MedLine Citation:
PMID:  22261541     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The cellular prion protein (PrP(c)) undergoes α-secretase-derived processing by disintegrins. This cleavage occurs within the 106-126 putative toxic domain of PrP(c), yielding two complementary N- and C-terminal fragments referred to as N1 and C1, respectively. Here we review our recent data showing that these two PrP(c)-derived products harbor distinct p53-dependent functions. Thus, C1 potentiates staurosporine (STS)-induced caspase-3 activation by upregulating p53 transcription, mRNA levels and activity. Conversely, N1 is protective both in vitro and in vivo. Thus, N1 inhibits STS-induced caspase-3 activation by downregulating p53 in various cell systems and protects rat retinal ganglion cells from hypoxia-induced apoptosis. Furthermore, N1 protects cells against C1-induced toxicity. Therefore, our data show that disintegrin-associated processing of PrP(c) gives rise to two fragments that display opposite effects on p53-dependent cell death and that can functionally interact.
Authors:
M-V Guillot-Sestier; F Checler
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-17
Journal Detail:
Title:  Neuro-degenerative diseases     Volume:  -     ISSN:  1660-2862     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101189034     Medline TA:  Neurodegener Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Affiliation:
Institut de Pharmacologie Moléculaire et Cellulaire et Institut de Neuromédecine Moléculaire, Equipe Labellisée Fondation pour la Recherche Médicale, Sophia-Antipolis, Valbonne, France.
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