Reference : TNFa and IKKb-mediated TANK/I-TRAF phosphorylation: implications for interaction with...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
TNFa and IKKb-mediated TANK/I-TRAF phosphorylation: implications for interaction with NEMO/IKKg and NF-kB activation
Bonif, Marianne [> >]
Meuwis, Marie-Alice mailto [Université de Liège - ULiège > > GIGA-Management : Plate-forme protéomique >]
Close, Pierre mailto [Université de Liège - ULiège > Département de pharmacie > Chimie médicale >]
Benoit, Valérie [> >]
Heyninck, Karen [> >]
Chapelle, Jean-Paul mailto [Centre Hospitalier Universitaire de Liège - CHU > > Chimie médicale >]
Bours, Vincent mailto [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 mailto [> >]
Beyaert, Rudi [> >]
Chariot, Alain mailto [Université de Liège - ULiège > Département de pharmacie > Chimie médicale >]
Biochemical Journal
Portland Press
Yes (verified by ORBi)
United Kingdom
[en] TANK/I-TRAF ; NF kappa B ; TNF
[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.
Giga-Signal Transduction
Researchers ; Professionals ; Students

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