Article (Scientific journals)
The c-jun N-terminal Kinase (JNK)-binding Protein (JNKBP1) Acts as a Negative Regulator of NOD2 Protein Signaling by Inhibiting Its Oligomerization Process
Lecat, Aurore; Di Valentin, Emmanuel; Somja, Joan et al.
2012In Journal of Biological Chemistry, 287 (35), p. 29213-26
Peer Reviewed verified by ORBi
 

Files


Full Text
Lecat JNKBP1 fin.pdf
Publisher postprint (3.35 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
JNKBP1; NOD2; Crohn's disease
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Immunology & infectious disease
Author, co-author :
Lecat, Aurore ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Di Valentin, Emmanuel  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Somja, Joan ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Jourdan, Samuel;  Université de Liège - ULiège > Sciences de la vie > CIP
Fillet, Marianne ;  Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Kufer, Thomas;  Université de Cologne > Institute for Medical Microbiology, Immunology and Hygiene
Habraken, Yvette ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Sadzot-Delvaux, Catherine ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Louis, Edouard  ;  Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie
Legrand-Poels, Sylvie ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Language :
English
Title :
The c-jun N-terminal Kinase (JNK)-binding Protein (JNKBP1) Acts as a Negative Regulator of NOD2 Protein Signaling by Inhibiting Its Oligomerization Process
Publication date :
2012
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
287
Issue :
35
Pages :
29213-26
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 19 June 2012

Statistics


Number of views
137 (50 by ULiège)
Number of downloads
6 (6 by ULiège)

Scopus citations®
 
20
Scopus citations®
without self-citations
19
OpenCitations
 
16

Bibliography


Similar publications



Contact ORBi