Reference : The c-jun N-terminal Kinase (JNK)-binding Protein (JNKBP1) Acts as a Negative Regulator ...
Scientific journals : Article
Human health sciences : Immunology & infectious disease
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/125587
The c-jun N-terminal Kinase (JNK)-binding Protein (JNKBP1) Acts as a Negative Regulator of NOD2 Protein Signaling by Inhibiting Its Oligomerization Process
English
Lecat, Aurore mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
Di Valentin, Emmanuel mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie et immunologie >]
Somja, Joan mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Jourdan, Samuel [Université de Liège - ULg > Sciences de la vie > CIP > >]
Fillet, Marianne mailto [Université de Liège - ULg > Département de pharmacie > Analyse des médicaments >]
Kufer, Thomas [Université de Cologne > Institute for Medical Microbiology, Immunology and Hygiene > > >]
Habraken, Yvette mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
Sadzot, Catherine mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie et immunologie >]
Louis, Edouard mailto [Université de Liège - ULg > Département des sciences cliniques > Hépato-gastroentérologie >]
Delvenne, Philippe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Piette, Jacques mailto [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie - Immunologie >]
Legrand-Poels, Sylvie mailto [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
2012
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
287
35
29213-26
Yes (verified by ORBi)
International
0021-9258
1083-351X
Baltimore
MD
[en] JNKBP1 ; NOD2 ; Crohn's disease
[en] NOD2 is one of the best characterized member of the cytosolic NOD-like receptors (NLR) family. NOD2 is able to sense muramyl dipeptide (MDP), a specific bacterial cell wall component, and to subsequently induce various signalling pathways leading to NF- kappaB activation and autophagy, both events contributing to an efficient innate and adaptative immune response. Interestingly, loss-of-function nod2 variants were associated with a higher susceptibility for Crohn ' s disease (CD), which highlights the physiological importance of proper regulation of NOD2 activity. We performed a biochemical screen to search for new NOD2 regulators. We identified a new NOD2 partner, c-jun N-terminal kinase binding protein 1 (JNKBP1), a scaffold protein characterized by a N-terminal WD-40 domain. JNKBP1, through its WD-40 domain, binds to NOD2 following MDP activation. This interaction attenuates NOD2-mediated NF-kappaB activation and IL-8 secretion as well as NOD2 antibacterial activity. JNKBP1 exerts its repressor effect by disturbing NOD2 oligomerization and RIP2 tyrosine phosphorylation, both steps required for downstream NOD2 signalling. We furthermore showed that JNKBP1 and NOD2 are co-expressed in the human intestinal epithelium and immune cells recruited in the lamina propria, which suggests that JNKBP1 contributes to maintain NOD2-mediated intestinal immune homeostasis.
http://hdl.handle.net/2268/125587
10.1074/jbc.M112.355545

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