Shigella IpaH0722 E3 Ubiquitin Ligase Effector Targets TRAF2 to Inhibit PKC-NF-κB Activity in Invaded Epithelial Cells

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. © 2013 ashida et al.