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Escherichia coli cytotoxic necrotizing factor 1 blocks cell cycle G2/M transition in uroepithelial cells
Loredana Falzano1, Perla Filippini, Sara Travaglione
1Department of Drug Research and Evaluation, Viale Regina Elena 299 00161, Rome, Italy.
Abstract:
Evidence is accumulating that a growing number of bacterial toxins act by modulating the eukaryotic cell cycle machinery. In this context, we provide evidence that a protein toxin named cytotoxic necrotizing factor 1 (CNF1) from uropathogenic Escherichia coli is able to block cell cycle G(2)/M transition in the uroepithelial cell line T24. CNF1 permanently activates the small GTP-binding proteins of the Rho family that, beside controlling the actin cytoskeleton organization, also play a pivotal role in a large number of other cellular processes, including cell cycle regulation. The results reported here show that CNF1 is able to induce the accumulation of cells in the G(2)/M phase by sequestering cyclin B1 in the cytoplasm and down-regulating its expression. The possible role played by the Rho GTPases in the toxin-induced cell cycle deregulation has been investigated and discussed. The activity of CNF1 on cell cycle progression can offer a novel view of E. coli pathogenicity.
Insights
Cytotoxic necrotizing factor 1 (CNF1) from E. coli blocks uroepithelial cell cycle progression. This bacterial toxin disrupts cell division by affecting Rho GTPases and cyclin B1, impacting E. coli pathogenicity.
Area of Science:
- Microbiology
- Cell Biology
- Toxicology
Background:
- Bacterial toxins increasingly target eukaryotic cell cycle machinery.
- Uropathogenic *Escherichia coli* (UPEC) produces cytotoxic necrotizing factor 1 (CNF1).
Purpose of the Study:
- To investigate CNF1's effect on the uroepithelial cell cycle.
- To elucidate the role of Rho GTPases in CNF1-mediated cell cycle disruption.
Main Methods:
- Cell cycle analysis of T24 uroepithelial cells treated with CNF1.
- Assessment of cyclin B1 localization and expression.
- Investigation of Rho GTPase family activation.
Main Results:
- CNF1 blocks G2/M cell cycle transition in T24 cells.
- CNF1 sequesters cyclin B1 in the cytoplasm and reduces its expression.
- CNF1 permanently activates Rho family GTPases.
Conclusions:
- CNF1 disrupts uroepithelial cell cycle progression by interfering with cyclin B1 regulation.
- Rho GTPase activation is implicated in CNF1-induced cell cycle deregulation.
- CNF1's impact on cell cycle offers insights into UPEC pathogenicity.
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