NR AUZH
AU Martin,S.F.; Herva,M.E.; Espinosa,J.C.; Parra,B.; Castilla,J.; Brun,A.; Torres,J.M.
TI Cell expression of a four extra octarepeat mutated PrPc modifies cell structure and cell cycle regulation
QU FEBS Letters 2006 Jul 24; 580(17): 4097-104
PT journal article
AB RK13 cell lines generated to express bovine PrPc with a four extra octarepeat insertional mutation (Bo-10ORPrPc) show partially insoluble PrPc and lower rates of cell growth when compared to either the same cells expressing wild type Bo-6ORPrPc or the original RK13 cell line. The expression of Bo-10ORPrPc 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-10ORPrPc, 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-10ORPrPc than those expressing Bo-6ORPrPc, while this effect was minimal or null in the original RK13 cell line. Hence, the presence of Bo-10ORPrPc in RK13 cells promotes cell cycle arrest at G2/M, and the effect is amplified by proteasome inhibition. These findings suggest a role for PrPc in cell morphology and cell cycle regulation, and open new avenues for understanding the mechanisms underlying PrP mutation-associated diseases.
MH 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; Research Support, Non-U.S. Gov't
AD Centro de Investigacion en Sanidad (CISA-INIA), Ctra. de Algete a El Casar, km. 8.100, 28130 Valdeolmos, Madrid, Spain.
SP englisch
PO Niederlande