A multinucleating Escherichia coli cytotoxin perturbs cell cycle in cultured epithelial cells.
Pathogenic Escherichia coli strains produce a number of virulence-associated factors, among which cytotoxic necrotizing factor 1 (CNF1). CNF1 is a chromosomally encoded toxin that permanently activates the small GTP-binding proteins of the Rho family (Rho, Rac and Cdc42) by catalizing their deamidation at a specific glutamine residue. This activation modulates a high number of cellular functions, including the reorganization of the actin cytoskeleton, the promotion of cell spreading and the multinucleation. Indeed, accumulating evidence indicates that, in addition to the well-characterized Ras GTPases, also Rho family proteins are crucial in different points of cell cycle regulation. Here, we report that CNF1 induces a block of the cell cycle at the G(2)/M transition in epithelial cell line HEp-2, and up-regulates cyclin B1 and p53 proteins confining them in the cytoplasm region. The ability of CNF1 to perturb cell cycle progression could play a role in E. coli pathogenicity.
Giamboi-Miraglia
A
A
Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Travaglione
S
S
Filippini
P
P
Fabbri
A
A
Fiorentini
C
C
Falzano
L
L
D001427:Bacterial Toxins / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019926:Cyclin B / Q000032:analysis; D056744:Cyclin B1; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000633:toxicity*; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D001427:Bacterial Toxins; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D029968:Escherichia coli Proteins; D016159:Tumor Suppressor Protein p53; C060296:cytotoxic necrotizing factor type 1