Article (Scientific journals)
TNFa and IKKb-mediated TANK/I-TRAF phosphorylation: implications for interaction with NEMO/IKKg and NF-kB activation
Bonif, Marianne; Meuwis, Marie-Alice; Close, Pierre et al.
2006In Biochemical Journal, 394, p. 593-603
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Keywords :
TANK/I-TRAF; NF kappa B; TNF
Abstract :
[en] Pro-inflammatory cytokines trigger signalling cascades leading to NF-kappaB (nuclear factor-kappaB)-dependent gene expression through IKK [IkappaB (inhibitory kappaB) kinase]-dependent phosphorylation and subsequent degradation of the IkappaB proteins and via induced phosphorylation of p65. These signalling pathways rely on sequentially activated kinases which are assembled by essential and non-enzymatic scaffold proteins into functional complexes. Here, we show that the pro-inflammatory cytokine TNFalpha (tumour necrosis factor alpha) promotes TANK [TRAF (TNF receptor-associated factor) family member associated NF-kappaB activator] recruitment to the IKK complex via a newly characterized C-terminal zinc finger. Moreover, we show that TANK is phosphorylated by IKKbeta upon TNFalpha stimulation and that this modification negatively regulates TANK binding to NEMO (NF-kappaB essential modulator). Interestingly, reduced TANK expression by RNA interference attenuates TNFalpha-mediated induction of a subset of NF-kappaB target genes through decreased p65 transactivation potential. Therefore the scaffold protein TANK is required for the cellular response to TNFalpha by connecting upstream signalling molecules to the IKKs and p65, and its subsequent IKKbeta-mediated phosphorylation may be a mechanism to terminate the TANK-dependent wave of NF-kappaB activation.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bonif, Marianne
Meuwis, Marie-Alice  ;  Université de Liège - ULiège > GIGA-Management : Plate-forme protéomique
Close, Pierre  ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Benoit, Valérie
Heyninck, Karen
Chapelle, Jean-Paul ;  Centre Hospitalier Universitaire de Liège - CHU > Chimie médicale
Bours, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Merville, Marie-Paule ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Piette, Jacques 
Beyaert, Rudi
Chariot, Alain ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Language :
English
Title :
TNFa and IKKb-mediated TANK/I-TRAF phosphorylation: implications for interaction with NEMO/IKKg and NF-kB activation
Publication date :
2006
Journal title :
Biochemical Journal
ISSN :
0264-6021
eISSN :
1470-8728
Publisher :
Portland Press, London, United Kingdom
Volume :
394
Pages :
593-603
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
FBC
ULg. ARC - Université de Liège. Actions de Recherche Concertées [BE]
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