1. Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1.
- Author
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Huelsenbeck SC, Roggenkamp D, May M, Huelsenbeck J, Brakebusch C, Rottner K, Ladwein M, Just I, Fritz G, Schmidt G, and Genth H
- Subjects
- Animals, Cell Death drug effects, Cell Shape drug effects, Enzyme Activation drug effects, Gene Expression Regulation drug effects, HT29 Cells, HeLa Cells, Humans, Mice, NIH 3T3 Cells, Polyploidy, Promoter Regions, Genetic genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Transcriptional Activation drug effects, Yersinia pseudotuberculosis metabolism, rac1 GTP-Binding Protein metabolism, rhoB GTP-Binding Protein genetics, Bacterial Toxins pharmacology, Cytoprotection drug effects, Escherichia coli metabolism, Escherichia coli Proteins pharmacology, rhoB GTP-Binding Protein metabolism
- Abstract
RhoB is the only member of the Rho subfamily of small GTPases, which is classified as an immediate early gene product. RhoB is up-regulated in response to growth factors as well as cytotoxic and genotoxic agents. Clostridial glucosylating toxins have been reported to evoke pronounced RhoB expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1, which positively regulates the activity of the rhoB promoter and RhoB expression. Conversely, the isomeric cytotoxic necrotizing factor from Yersinia pseudotuberculosis (CNFy) drives GTP-loading of basal RhoB but fails to cause activation of the rhoB promoter and thus its expression. CNF1 inhibits cytokinesis and induces the formation of bi-nucleated (tetraploid) cells. Upon long term treatment with CNF1, RhoB(-/-) mouse embryonic fibroblasts (MEFs) exhibit DNA fragmentation, phosphatidylserine exposure, and loss of membrane integrity, while RhoB(+/-) MEFs persist as bi-nucleated (tetraploid) cells without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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