Bacterial toxins activating Rho GTPases.
The CNF1 toxin is produced by some uropathogenic (UPECs) andmeningitis-causing Escherichia coli strains. It belongs to a large family of bacterial virulence factors and toxins modifying cellular regulators of the actin cytoskeleton, namely the Rho GTPases. CNF1 autonomously enters the host cell cytosol, where it catalyzes the constitutive activation of Rho GTPases by deamidation. This activation is, however, attenuated because of activated Rho protein ubiquitin-mediated proteasomal degradation. Both Rho protein activation and deactivation confer phagocytic properties on epithelial and endothelial cells, as well as epithelial cell motility and cell-cell junction dynamics. Transcriptome analysis using DNA microarray revealed that endothelial cells respond to high doses of CNF1 by launching a genetic program of host alarm. This host cell reaction to CNF1 intoxication also indicates that degradation of activated Rho proteins by the proteasome may lead to a lowering of the threshold of the intoxicated cell inflammatory response. These results are consistent with growing evidence that Rho proteins control the cell inflammatory responses. It is tempting to assume that Rho deregulation may participate in various immunological disorders also involved in cancer.
Munro
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Faculté de Médecine, 1/INSERM, U627, 28 Avenue de Valombrose, 06107 Nice, France.
Lemichez
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D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000633:toxicity; D003603:Cytotoxins / Q000633:toxicity; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000633:toxicity; D006801:Humans; D037521:Virulence Factors / Q000633:toxicity; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D001427:Bacterial Toxins; D003603:Cytotoxins; D020536:Enzyme Activators; D029968:Escherichia coli Proteins; D037521:Virulence Factors; C060296:cytotoxic necrotizing factor type 1; D020741:rho GTP-Binding Proteins