Charité-University Medicine Berlin, Institute of Physiology, Thielallee 71, D-14195 Berlin, Germany.
Differentiation. 2011 Feb;81(2):99-106. doi: 10.1016/j.diff.2010.11.002. Epub 2010 Dec 4.
We could recently demonstrate an important role of receptor interacting protein-2 (RIP2), an activator of nuclear factor kappa B (NF-κB) and a target of activated receptors of the tumor necrosis factor receptor (TNFR) type, in myogenic differentiation and regeneration. Here, we analyze a potential role of TNFR associated factor 6 (TRAF6), which also associates with the cytoplasmic domain of TNFR type, but also IL-1-R and TLR type receptors, and activates NF-κB, in these processes. Specifically, we show that during myogenic differentiation in vitro, traf6 gene expression is downregulated in normal myoblasts, but not in rhabdomyosarcoma cells, suggesting a role of the TRAF6 protein in this process. Inhibition of traf6 expression using specific siRNAs led to an inhibition of both myoblast proliferation and differentiation, whereas inhibition of the TRAF6 effector NF-κB alone in our system only blocked proliferation. Finally, we demonstrate that the traf6 gene is downregulated in skeletal muscle tissue of the dystrophic mdx mouse. Taken together, these data argue for a role of TRAF6 in the regulation of skeletal muscle differentiation and regeneration.
我们最近证明了受体相互作用蛋白 2（RIP2）在肌生成分化和再生中的重要作用，它是核因子 kappa B（NF-κB）的激活剂，也是肿瘤坏死因子受体（TNFR）类型的激活受体的靶标。在这里，我们分析了 TNFR 相关因子 6（TRAF6）的潜在作用，TRAF6 也与 TNFR 类型的细胞质结构域以及 IL-1-R 和 TLR 类型的受体结合，并激活 NF-κB，在这些过程中。具体来说，我们发现在体外肌生成分化过程中，正常成肌细胞中 traf6 基因表达下调，但横纹肌肉瘤细胞中未下调，表明 TRAF6 蛋白在此过程中发挥作用。使用特异性 siRNAs 抑制 traf6 表达会导致成肌细胞增殖和分化均受到抑制，而在我们的系统中仅抑制 TRAF6 效应物 NF-κB 会阻止增殖。最后，我们证明了在营养不良性 mdx 小鼠的骨骼肌组织中 traf6 基因下调。综上所述，这些数据表明 TRAF6 在调节骨骼肌分化和再生中起作用。
