Escherichia coli cytotoxic necrotizing factor 1 blocks cell cycle G2/M transition in uroepithelial cells.
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.
Falzano
Loredana
L
Department of Drug Research and Evaluation, Viale Regina Elena 299 00161, Rome, Italy.
Filippini
Perla
P
Travaglione
Sara
S
Miraglia
Alessandro Giamboi
AG
Fabbri
Alessia
A
Fiorentini
Carla
C
D001427:Bacterial Toxins; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D003603:Cytotoxins / Q000502:physiology*; D004926:Escherichia coli / Q000472:pathogenicity / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000502:physiology*; D016195:G2 Phase / Q000502:physiology*; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D001743:Urinary Bladder / Q000166:cytology* / Q000382:microbiology*; D019459:Urothelium / Q000382:microbiology; D020741:rho GTP-Binding Proteins / Q000502:physiology
D001427:Bacterial Toxins; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D003603:Cytotoxins; D029968:Escherichia coli Proteins; D006131:Growth Inhibitors; C060296:cytotoxic necrotizing factor type 1; D020741:rho GTP-Binding Proteins