A role for NRAGE in NF-kappaB activation through the non-canonical BMP pathway.

BMC Biology
Nicholas N MatlukJ M Verdi

Abstract

Previous studies have linked neurotrophin receptor-interacting MAGE protein to the bone morphogenic protein signaling pathway and its effect on p38 mediated apoptosis of neural progenitor cells via the XIAP-Tak1-Tab1 complex. Its effect on NF-kappaB has yet to be explored. Herein we report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -alpha/beta and subsequent transcriptional activation of the p65 subunit of NF-kappaB. Ablation of endogenous NRAGE by siRNA inhibited NF-kappaB pathway activation, while ablation of Tak1 and Tab1 by morpholino inhibited overexpression of NRAGE from activating NF-kappaB. Finally, cytokine profiling of an NRAGE over-expressing stable line revealed the expression of macrophage migration inhibitory factor. Modulation of NRAGE expression revealed novel roles in regulating NF-kappaB activity in the non-canonical bone morphogenic protein signaling pathway. The expression of macrophage migration inhibitory factor by bone morphogenic protein -4 reveals novel crosstalk between an immune cytokine and a developmental pathway.

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Citations

Oct 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ge ZhangXiaoying Xue
Oct 12, 2016·Molecular Therapy. Nucleic Acids·Tommy A KarlsenJan E Brinchmann
May 17, 2018·Tissue Engineering. Part a·Juliane D GlaeserHyun W Bae
Apr 11, 2012·Developmental Neurobiology·Allison M BondJohn A Kessler
Jan 11, 2013·BMC Genomics·Chia-Lang Hsu, Ueng-Cheng Yang
Sep 15, 2020·The Journal of Biological Chemistry·Rebecca R Florke GeePatrick Ryan Potts
Aug 1, 2021·Metabolism: Clinical and Experimental·Gabriel S JensenKristy L Townsend

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Methods Mentioned

BETA
two hybrid
transfection
ubiquitination
Protein Array
Dot blot
transgenic
nuclear translocation
immunoprecipitation
Assay
dissections

Software Mentioned

MetaMorph

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