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 J, May M, Schulz F, Schelle I, Ronkina N, Hohenegger M, Fritz G, Just I, Gerhard R, and Genth H
- Subjects
- Animals, Apoptosis drug effects, Bacterial Toxins metabolism, Caspases metabolism, Enzyme Activation drug effects, Fibroblasts metabolism, Glycosylation drug effects, Mice, NIH 3T3 Cells, Phosphatidylinositol 3-Kinases metabolism, Proteolysis drug effects, Signal Transduction drug effects, Transcriptional Activation drug effects, p38 Mitogen-Activated Protein Kinases metabolism, ras Proteins antagonists & inhibitors, Bacterial Toxins toxicity, Clostridium sordellii chemistry, Fibroblasts cytology, Fibroblasts drug effects, Gene Expression Regulation, Enzymologic drug effects, ras Proteins metabolism, rhoB GTP-Binding Protein genetics
- 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 p38(alpha) 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 © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
- Published
- 2012
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