NRAGE 通过非经典 BMP 途径在 NF-κB 激活中的作用。

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

机构信息

Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.

出版信息

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

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.

背景

先前的研究将神经生长因子受体相互作用的 Mage 蛋白与骨形态发生蛋白信号通路联系起来，其通过 XIAP-Tak1-Tab1 复合物影响 p38 介导的神经祖细胞凋亡。其对 NF-κB 的影响尚未得到探索。

结果

在此，我们报告 NRAGE 通过相同的 XIAP-Tak1-Tab1 复合物，需要 IKK-α/β的磷酸化，随后 NF-κB 的 p65 亚基的转录激活。通过 siRNA 敲除内源性 NRAGE 抑制 NF-κB 途径的激活，而通过 morpholino 敲除 Tak1 和 Tab1 抑制 NRAGE 的过表达激活 NF-κB。最后，对过表达 NRAGE 的稳定系进行细胞因子分析，发现巨噬细胞移动抑制因子的表达。