Shigella IpaH0722 E3 Ubiquitin Ligase Effector Targets TRAF2 to Inhibit PKC–NF-κB Activity in Invaded Epithelial Cells |
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| Authors: | Hiroshi Ashida Hiroyasu Nakano Chihiro Sasakawa |
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| Institution: | 1. Division of Bacterial Infection Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.; 2. Department of Immunology, Juntendo University School Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.; 3. Nippon Institute for Biological Science, Shinmachi, Ome, Tokyo, Japan.; 4. Medical Mycology Research Center, Chiba University, Inohana, Chuo-ku, Chiba, Japan.; Collège de France, France, |
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| Abstract: | NF-κB plays a central role in modulating innate immune responses to bacterial infections. Therefore, many bacterial pathogens deploy multiple mechanisms to counteract NF-κB activation. The invasion of and subsequent replication of Shigella within epithelial cells is recognized by various pathogen recognition receptors as pathogen-associated molecular patterns. These receptors trigger innate defense mechanisms via the activation of the NF-κB signaling pathway. Here, we show the inhibition of the NF-κB activation by the delivery of the IpaH E3 ubiquitin ligase family member IpaH0722 using Shigella''s type III secretion system. IpaH0722 dampens the acute inflammatory response by preferentially inhibiting the PKC-mediated activation of NF-κB by ubiquitinating TRAF2, a molecule downstream of PKC, and by promoting its proteasome-dependent degradation. |
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