| Cell expression of a four extra octarepeat mutated PrPC modifies cell structure and cell cycle regulation. | |
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MedLine Citation:
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PMID: 16828087 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sergio F Martín; María E Herva; Juan-Carlos Espinosa; Beatriz Parra; Joaquín Castilla; Alejandro Brun; Juan M Torres |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-06-30 |
Journal Detail:
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Title: FEBS letters Volume: 580 ISSN: 0014-5793 ISO Abbreviation: FEBS Lett. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-07-17 Completed Date: 2006-08-28 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0155157 Medline TA: FEBS Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 4097-104 Citation Subset: IM |
Affiliation:
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Centro de Investigación en Sanidad (CISA-INIA), Ctra. de Algete a El Casar, km. 8.100, 28130 Valdeolmos, Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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