Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

Research output: Contribution to journalJournal articlepeer-review

  • Stefanie C Huelsenbeck
  • Dennis Roggenkamp
  • Martin May
  • Johannes Huelsenbeck
  • Brakebusch, Cord Herbert
  • Klemens Rottner
  • Markus Ladwein
  • Ingo Just
  • Gerhard Fritz
  • Gudula Schmidt
  • Harald Genth
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.
Original languageEnglish
JournalInternational Journal of Biochemistry & Cell Biology
Volume45
Issue number8
Pages (from-to)1767-75
Number of pages9
ISSN1357-2725
DOIs
Publication statusPublished - Aug 2013

    Research areas

  • Animals, Bacterial Toxins, Cell Death, Cell Shape, Cytoprotection, Enzyme Activation, Escherichia coli, Escherichia coli Proteins, Gene Expression Regulation, HT29 Cells, HeLa Cells, Humans, Mice, NIH 3T3 Cells, Polyploidy, Promoter Regions, Genetic, RNA, Messenger, Transcriptional Activation, Yersinia pseudotuberculosis, rac1 GTP-Binding Protein, rhoB GTP-Binding Protein

ID: 108162839