1. Cytoprotective effect of the small GTPase RhoB expressed upon treatment of fibroblasts with the Ras-glucosylating Clostridium sordellii lethal toxin
- Author
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Huelsenbeck, Johannes, May, Martin, Schulz, Florian, Schelle, Ilona, Ronkina, Natalia, Hohenegger, Martin, Fritz, Gerhard, Just, Ingo, Gerhard, Ralf, and Genth, Harald
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GUANOSINE triphosphatase , *RHO factor , *FIBROBLASTS , *RAS proteins , *CLOSTRIDIUM , *TOXINS , *FARNESYLTRANSFERASE - Abstract
Abstract: Mono-glucosylation of (H/K/N)Ras by Clostridium sordellii lethal toxin (TcsL) blocks critical survival signaling pathways, resulting in apoptosis. In this study, TcsL and K-Ras knock-down by siRNA are presented to result in expression of the cell death-regulating small GTPase RhoB. TcsL-induced RhoB expression is based on transcriptional activation involving p38alpha MAP kinase. Newly synthesized RhoB protein is rapidly degraded in a proteasome- and a caspase-dependent manner, providing first evidence for caspase-dependent degradation of a Rho family protein. Although often characterised as a pro-apoptotic protein, RhoB suppresses caspase-3 activation in TcsL-treated fibroblasts. The finding on the cytoprotective activity of RhoB in TcsL-treated cells re-enforces the concept that RhoB exhibits cytoprotective rather than pro-apoptotic activity in a cellular background of inactive Ras. [Copyright &y& Elsevier]
- Published
- 2012
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