FBXW7α attenuates inflammatory signalling by downregulating C/EBPδ and its target gene Tlr4.

Détails

ID Serval
serval:BIB_74C4B858B27D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
FBXW7α attenuates inflammatory signalling by downregulating C/EBPδ and its target gene Tlr4.
Périodique
Nature Communications
Auteur(s)
Balamurugan K., Sharan S., Klarmann K.D., Zhang Y., Coppola V., Summers G.H., Roger T., Morrison D.K., Keller J.R., Sterneck E.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
2013
Volume
4
Pages
1662
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Toll-like receptor 4 (Tlr4) has a pivotal role in innate immune responses, and the transcription factor CCAAT/enhancer binding protein delta (C/EBPδ, Cebpd) is a Tlr4-induced gene. Here we identify a positive feedback loop in which C/EBPδ activates Tlr4 gene expression in macrophages and tumour cells. In addition, we discovered a negative feedback loop whereby the tumour suppressor FBXW7α (FBW7, Cdc4), whose gene expression is inhibited by C/EBPδ, targets C/EBPδ for degradation when C/EBPδ is phosphorylated by GSK-3β. Consequently, FBXW7α suppresses Tlr4 expression and responses to the ligand lipopolysaccharide. FBXW7α depletion alone is sufficient to augment pro-inflammatory signalling in vivo. Moreover, as inflammatory pathways are known to modulate tumour biology, Cebpd null mammary tumours, which have reduced metastatic potential, show altered expression of inflammation-associated genes. Together, these findings reveal a role for C/EBPδ upstream of Tlr4 signalling and uncover a function for FBXW7α as an attenuator of inflammatory signalling.
Pubmed
Web of science
Création de la notice
06/05/2013 15:23
Dernière modification de la notice
03/03/2018 18:22
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