A large number of bacterial toxins catalyze post-translational modifications of small GTPases of the Ras superfamily. Some Gram-negative bacteria such as Escherichia coli, Yersinia pseudotuberculosis, and Bordetella spp produce deamidase toxins capable of catalyzing the post-translational modification of a critical glutamine residue of Rho GTPases into a glutamic acid. This type of targeted modification of Rho GTPases is analogous to a somatic mutation leading to the permanent activation of Rho GTPases. We have discovered a cellular regulation by ubiquitination and proteasomal degradation that ensures a proper control of the level of activation of these GTPases. We currently decipher the elements of this signaling system considering its importance in the control of cell division and migration, cohesion of epithelia and inflammatory reactions as well as its involvement in the mechanism of action of toxins. A growing number of studies point to the implication of a dysfunction of this system in infectious, inflammatory and tumorigenesis processes. We study in parallel the mode of action of the glucosylating toxins of Clostridium, which induce the inactivation of these GTPases.