A role for NRAGE in NF-kappaB activation through the non-canonical BMP pathway.
Center for Molecular Medicine, Maine Medical Center Research Institute
BMC biology [electronic resource]
Animals, Antigens, Neoplasm, Blotting, Western, Bone Morphogenetic Protein 4, Bone Morphogenetic Proteins, Cell Line, Cell Line, Tumor, Humans, I-kappa B Kinase, Immunohistochemistry, Immunoprecipitation, Kidney, Macrophage Migration-Inhibitory Factors, Mice, Mice, Transgenic, Neoplasm Proteins, Phosphorylation, RNA, Small Interfering, Signal Transduction, Transcription Factor RelA
BACKGROUND: 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.
RESULTS: 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.
CONCLUSION: 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.
Matluk, Nicholas; Rochira, Jennifer A; Karaczyn, Aldona; Adams, Tamara; and Verdi, Joseph M, "A role for NRAGE in NF-kappaB activation through the non-canonical BMP pathway." (2010). Maine Medical Center. 2185.