| α-Secretase-Derived Cleavage of Cellular Prion Yields Biologically Active Catabolites with Distinct Functions. | |
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MedLine Citation:
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PMID: 22261541 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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M-V Guillot-Sestier; F Checler |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-17 |
Journal Detail:
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Title: Neuro-degenerative diseases Volume: - ISSN: 1660-2862 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101189034 Medline TA: Neurodegener Dis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 S. Karger AG, Basel. |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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