Document Detail


Cell expression of a four extra octarepeat mutated PrPC modifies cell structure and cell cycle regulation.
MedLine Citation:
PMID:  16828087     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RK13 cell lines generated to express bovine PrP(C) with a four extra octarepeat insertional mutation (Bo-10ORPrP(C)) show partially insoluble PrP(C) and lower rates of cell growth when compared to either the same cells expressing wild type Bo-6ORPrP(C) or the original RK13 cell line. The expression of Bo-10ORPrP(C) in cell cultures was also associated with changes in cell size and reorganization of the actin cytoskeleton. This last process was reversed by Clostridium difficile toxin-B, a specific inhibitor of small GTPase proteins. Further, in clones expressing Bo-10ORPrP(C), increased proportions of cells at cell cycle stage G2/M were observed. Proteasome inhibitors caused a further expansion of G2/M-stage cells that was more marked in cell lines expressing Bo-10ORPrP(C) than those expressing Bo-6ORPrP(C), while this effect was minimal or null in the original RK13 cell line. Hence, the presence of Bo-10ORPrP(C) in RK13 cells promotes cell cycle arrest at G2/M, and the effect is amplified by proteasome inhibition. These findings suggest a role for PrP(C) in cell morphology and cell cycle regulation, and open new avenues for understanding the mechanisms underlying PrP mutation-associated diseases.
Authors:
Sergio F Martín; María E Herva; Juan-Carlos Espinosa; Beatriz Parra; Joaquín Castilla; Alejandro Brun; Juan M Torres
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-30
Journal Detail:
Title:  FEBS letters     Volume:  580     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-17     Completed Date:  2006-08-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  4097-104     Citation Subset:  IM    
Affiliation:
Centro de Investigación en Sanidad (CISA-INIA), Ctra. de Algete a El Casar, km. 8.100, 28130 Valdeolmos, Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Toxins / pharmacology
Cattle
Cell Division* / drug effects,  genetics
Cell Line
Cell Shape / drug effects
Enzyme Activation
G2 Phase* / drug effects,  genetics
Monomeric GTP-Binding Proteins / antagonists & inhibitors,  metabolism
Mutation*
PrPC Proteins / genetics,  metabolism*
Prion Diseases / genetics
Protease Inhibitors / pharmacology
Proteasome Endopeptidase Complex / antagonists & inhibitors,  metabolism
Rabbits
Chemical
Reg. No./Substance:
0/Bacterial Toxins; 0/Clostridium difficile lethal toxin B; 0/PrPC Proteins; 0/Protease Inhibitors; EC 3.4.25.1/Proteasome Endopeptidase Complex; EC 3.6.5.2/Monomeric GTP-Binding Proteins

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