Document Detail

Two-steps control of cellular prion physiology by the extracellular regulated kinase-1 (ERK1).
MedLine Citation:
PMID:  22453173     Owner:  NLM     Status:  MEDLINE    
Cellular prion (PrP(c)) undergoes a regulated α-secretase-like cleavage by the disintegrin ADAM17 similar to the one taking place on β-amyloid precursor protein (βAPP). Because these cleavages give rise to biologically active fragments, understanding their regulation could be of importance. We have established that the Extracellular Regulated Kinase-1 (ERK1) controls PrPc processing by modulating ADAM17 phosphorylation in a protein kinase C-dependent manner. Strikingly, we also demonstrated that ERK1 acts upstream to increase PrP(c) promoter transactivation in an AP-1 dependent manner. Therefore, ERK1 exerts a dual control of both PrP(c) metabolism and expression. Interestingly, α-secretase cleavage of βAPP appears to be independent of ERK1. I describe here similarities and differences in α-secretase-mediated PrP(c) and βAPP processing pathways and discuss putative physiopathological implications.
Frédéric Checler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Prion     Volume:  6     ISSN:  1933-690X     ISO Abbreviation:  Prion     Publication Date:    2012 Jan-Mar
Date Detail:
Created Date:  2012-03-28     Completed Date:  2012-08-10     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101472305     Medline TA:  Prion     Country:  United States    
Other Details:
Languages:  eng     Pagination:  23-5     Citation Subset:  IM    
Institut de Pharmacologie Moléculaire et Cellulaire and Institut de NeuroMédecine Moléculaire, Equipe labellisée Fondation pour la Recherche Médicale, Valbonne, France.
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MeSH Terms
ADAM Proteins / metabolism
Amyloid beta-Protein Precursor / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism*
Models, Biological
Prions / physiology*
Protein Processing, Post-Translational
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/Prions; EC Protein Kinase 3; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/tumor necrosis factor-alpha convertase

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