%0 Journal Article
%T The Inositol Phosphatase SHIP-1 Inhibits NOD2-Induced NF-¦ĘB Activation by Disturbing the Interaction of XIAP with RIP2
%A Claude Cond¨¦
%A Xavier Rambout
%A Marielle Lebrun
%A Aurore Lecat
%A Emmanuel Di Valentin
%A Franck Dequiedt
%A Jacques Piette
%A Geoffrey Gloire
%A Sylvie Legrand
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0041005
%X SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-¦ĘB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-¦ĘB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-¦ĘB signaling.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0041005