We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cell expression of a four extra octarepeat mutated PrP<sup>C</sup> modifies cell structure and cell cycle regulation
- Authors
Martín, Sergio F.; Herva, María E.; Espinosa, Juan-Carlos; Parra, Beatriz; Castilla, Joaquín; Brun, Alejandro; Torres, Juan M.
- Abstract
Abstract: 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.
- Subjects
CELL lines; APOPTOSIS; CLOSTRIDIOIDES difficile; CELLULAR control mechanisms
- Publication
FEBS Letters, 2006, Vol 580, Issue 17, p4097
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2006.06.054