title: Cytoprotective effect of the small GTPase RhoB expressed upon treatment of fibroblasts with the Ras-glucosylating Clostridium sordellii lethal toxin.
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.
authors.affiliation: Institute of Toxicology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Huelsenbeck
authors.forename: Martin
authors.initials: M
authors.lastname: May
authors.forename: Florian
authors.initials: F
authors.lastname: Schulz
authors.forename: Ilona
authors.initials: I
authors.lastname: Schelle
authors.forename: Natalia
authors.initials: N
authors.lastname: Ronkina
authors.forename: Martin
authors.initials: M
authors.lastname: Hohenegger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fritz
authors.forename: Ingo
authors.initials: I
authors.lastname: Just
authors.forename: Ralf
authors.initials: R
authors.lastname: Gerhard
authors.forename: Harald
authors.initials: H
authors.lastname: Genth
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D047989:Paraclostridium sordellii / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006031:Glycosylation / Q000187:drug effects; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000235:genetics*
chemical_list: D001427:Bacterial Toxins; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D018631:ras Proteins; D020743:rhoB GTP-Binding Protein