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

BMC Biol. 2010 Jan 25;8:7. doi: 10.1186/1741-7007-8-7.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Blotting, Western
  • Bone Morphogenetic Protein 4 / pharmacology
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • I-kappa B Kinase / metabolism
  • Immunohistochemistry
  • Immunoprecipitation
  • Kidney / metabolism
  • Macrophage Migration-Inhibitory Factors / genetics
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Phosphorylation / drug effects
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / physiology
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*

Substances

  • Antigens, Neoplasm
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • MAGED1 protein, human
  • Macrophage Migration-Inhibitory Factors
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Transcription Factor RelA
  • I-kappa B Kinase