title: The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2.
abstract: 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-κB 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-κB 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-κB signaling.
authors: Laboratory of Virology and Immunology, Signal Transduction Unit, GIGA-R, University of Liège, Liège, Belgium.
authors: Claude
authors: C
authors: Condé
authors: Xavier
authors: X
authors: Rambout
authors: Marielle
authors: M
authors: Lebrun
authors: Aurore
authors: A
authors: Lecat
authors: Emmanuel
authors: E
authors: Di Valentin
authors: Franck
authors: F
authors: Dequiedt
authors: Jacques
authors: J
authors: Piette
authors: Geoffrey
authors: G
authors: Gloire
authors: Sylvie
authors: S
authors: Legrand
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System; D007249:Inflammation; D000072181:Inositol Polyphosphate 5-Phosphatases; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism*; D015398:Signal Transduction; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases