close

CNF1 exploits the ubiquitin-proteasome machinery to restrict Rho GTPase activation for bacterial host cell invasion

Doye, A.; Mettouchi, A.; Bossis, G.; Clement, R.; Buisson-Touati, C.; Flatau, G.; Gagnoux, L.; Piechaczyk, M.; Boquet, P.; Lemichez, E.

Cell

2002-11-15 / vol 111 / pages 553-564

Abstract

CNF1 toxin is a virulence factor produced by uropathogenic Escherichia coli. Upon cell binding and introduction into the cytosol, CNF1 deamidates glutamine 63 of RhoA (or 61 of Rac and Cdc42), rendering constitutively active these GTPases. Unexpectedly, we measured in bladder cells a transient CNF1-induced activation of Rho GTPases, maximal for Rac. Deactivation of Rac correlated with the increased susceptibility of its deamidated form to ubiquitin/proteasome-mediated degradation. Sensitivity to ubiquitylation could be generalized to other permanent-activated forms of Rac and to its sustained activation by Dbl. Degradation of the toxin-activated Rac allowed both host cell motility and efficient cell invasion by uropathogenic bacteria. CNF1 toxicity thus results from a restricted activation of Rho GTPases through hijacking the host cell proteasomal machinery.

0092-8674

Tags

protein; binding; actin cytoskeleton; domain; cytotoxic necrotizing factor-1; deamidation; factor type-1; toxin; urinary-tract infections; uropathogenic escherichia-coli

Back to all publications