NOTCH1 can initiate NF-κB activation via cytosolic interactions with components of the T cell Signalosome.

Détails

Ressource 1Télécharger: BIB_8263EB04C4BB.P001.pdf (1996.60 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_8263EB04C4BB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
NOTCH1 can initiate NF-κB activation via cytosolic interactions with components of the T cell Signalosome.
Périodique
Frontiers in Immunology
Auteur(s)
Shin H.M., Tilahun M.E., Cho O.H., Chandiran K., Kuksin C.A., Keerthivasan S., Fauq A.H., Golde T.E., Miele L., Thome M., Osborne B.A., Minter L.M.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Statut éditorial
Publié
Date de publication
2014
Volume
5
Pages
249
Langue
anglais
Résumé
T cell stimulation requires the input and integration of external signals. Signaling through the T cell receptor (TCR) is known to induce formation of the membrane-tethered CBM complex, comprising CARMA1, BCL10, and MALT1, which is required for TCR-mediated NF-κB activation. TCR signaling has been shown to activate NOTCH proteins, transmembrane receptors also implicated in NF-κB activation. However, the link between TCR-mediated NOTCH signaling and early events leading to induction of NF-κB activity remains unclear. In this report, we demonstrate a novel cytosolic function for NOTCH1 and show that it is essential to CBM complex formation. Using a model of skin allograft rejection, we show in vivo that NOTCH1 acts in the same functional pathway as PKCθ, a T cell-specific kinase important for CBM assembly and classical NF-κB activation. We further demonstrate in vitro NOTCH1 associates physically with PKCθ and CARMA1 in the cytosol. Unexpectedly, when NOTCH1 expression was abrogated using RNAi approaches, interactions between CARMA1, BCL10, and MALT1 were lost. This failure in CBM assembly reduced inhibitor of kappa B alpha phosphorylation and diminished NF-κB-DNA binding. Finally, using a luciferase gene reporter assay, we show the intracellular domain of NOTCH1 can initiate robust NF-κB activity in stimulated T cells, even when NOTCH1 is excluded from the nucleus through modifications that restrict it to the cytoplasm or hold it tethered to the membrane. Collectively, these observations provide evidence that NOTCH1 may facilitate early events during T cell activation by nucleating the CBM complex and initiating NF-κB signaling.
Mots-clé
CARMA1, NF-κB, NOTCH1, PKCθ, T cell subject category: immunology, cytosolic, non-canonical, signal transduction
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/12/2014 16:29
Dernière modification de la notice
08/05/2019 21:12
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