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MBC in Press, published online ahead of print May 16, 2007
Mol. Biol. Cell 10.1091/mbc.E06-10-0910

A more recent version of this article appeared on July 1, 2007
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Submitted on October 11, 2006
Revised on March 28, 2007
Accepted on May 3, 2007

Cytotoxic Necrotizing Factor 1 Prevents Apoptosis via the AKT/IKK Pathway: Role of NF-{kappa}B and Bcl-2

Alessandro Giamboi Miraglia,* Sara Travaglione,* Stefania Meschini,{dagger} Loredana Falzano,* Paola Matarrese,* Maria Giovanna Quaranta,* Marina Viora,* Carla Fiorentini,*{ddagger} and Alessia Fabbri*{ddagger}

Departments of *Drug Research and Evaluation and {dagger}Technology and Health, Istituto Superiore di Sanità, 00161 Rome, Italy

Monitoring Editor: Ralph Isberg

Cytotoxic Necrotizing Factor 1 (CNF1) is a protein toxin produced by some pathogenic strains of Escherichia coli that specifically activates Rho, Rac and Cdc42 GTPases. We previously reported that this toxin prevents the UVB-induced apoptosis in epithelial cells, with a mechanism that remained to be defined. In this work, we show that the proteasomal degradation of the Rho GTPase is necessary to achieve cell death protection, since inhibition of Rho degradation abolishes the prosurvival activity of CNF1. We hypothesize that Rho inactivation allows the activity of Rac to become dominant. This in turn leads to stimulation of the PI3K/Akt/IKK/NF-{kappa}B prosurvival pathway and to a remarkable modification in the architecture of the mitochondrial network, mainly consisting in the appearance of elongated and interconnected mitochondria. Importantly we found that Bcl-2 silencing reduces the ability of CNF1 to protect cells against apoptosis and also prevents the CNF1-induced mitochondrial changes. It is worth noting that the ability of a bacterial toxin to induce such a remodeling of the mitochondrial network is herein reported for the first time. The possible pathophysiological relevance of this finding is discussed.

{ddagger}C.F. and A.F. were principal investigators.

Address correspondence to: Carla Fiorentini (carla.fiorentini{at}iss.it)




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T. J. Wiles, B. K. Dhakal, D. S. Eto, and M. A. Mulvey
Inactivation of Host Akt/Protein Kinase B Signaling by Bacterial Pore-forming Toxins
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[Abstract] [Full Text] [PDF]


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