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

Details

Serval ID
serval:BIB_74C4B858B27D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
FBXW7α attenuates inflammatory signalling by downregulating C/EBPδ and its target gene Tlr4.
Journal
Nature Communications
Author(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
Publication state
Published
Issued date
2013
Volume
4
Pages
1662
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
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
Open Access
Yes
Create date
06/05/2013 14:23
Last modification date
20/08/2019 14:32
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