A role for NRAGE in NF-κB activation through the non-canonical BMP pathway
1 Maine Medical Center Research Institute, Center for Molecular Medicine, 81 Research Drive, Scarborough, Maine 04074, USA
2 Graduate School of Biomedical Sciences, The University of Maine at Orono, 267A Engineering and Science Research Building, Orono, Maine, 04469 USA
3 Functional Genomics IGERT Program, 263 Engineering and Research Science Building, The University of Maine at Orono, Orono, Maine, 04469 USA
BMC Biology 2010, 8:7 doi:10.1186/1741-7007-8-7Published: 25 January 2010
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-κB has yet to be explored.
Herein we report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -α/β and subsequent transcriptional activation of the p65 subunit of NF-κB. Ablation of endogenous NRAGE by siRNA inhibited NF-κB pathway activation, while ablation of Tak1 and Tab1 by morpholino inhibited overexpression of NRAGE from activating NF-κB. 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-κB 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.