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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB.
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TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB.

机译：TRAF6独特地介导MyD88和IRAK-1诱导的NF-κB活化。

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摘要

MyD88 and IL-1R-associated kinase 1 (IRAK-1) play crucial roles as adaptor molecules in signal transduction of the TLR/IL-1R superfamily, and it is known that expression of these proteins leads to the activation of NF-kappaB in a TNFR-associated factor 6 (TRAF6)-dependent manner. We found in this study, however, that a dominant-negative mutant of TRAF6, lacking the N-terminal RING and zinc-finger domain, did not inhibit IRAK-1-induced activation of NF-kappaB in human embryonic kidney 293 cells, although the TRAF6 mutant strongly suppressed the MyD88-induced activation. The dominant-negative mutant of TRAF6 did not affect the IRAK-1-induced activation, regardless of the expression level of IRAK-1. In contrast, small interfering RNA silencing of TRAF6 expression inhibited MyD88-induced and IRAK-1-induced activation, and supplementation with the TRAF6 dominant-negative mutant did not restore the IRAK-1-induced activation. Expression of IRAK-1, but not MyD88, induced the oligomerization of TRAF6, and IRAK-1 and the TRAF6 dominant-negative mutant were associated with TRAF6. These results indicate that TRAF6 is involved but with different mechanisms in MyD88-induced and IRAK-induced activation of NF-kappaB and suggest that TRAF6 uses a distinctive mechanism to activate NF-kappaB depending on signals.
机译：MyD88和IL-1R相关激酶1（IRAK-1）在TLR / IL-1R超家族的信号转导中作为衔接分子发挥关键作用，众所周知，这些蛋白的表达会导致NF-κB的活化。 TNFR相关因子6（TRAF6）依赖的方式。然而，我们在这项研究中发现，TRAF6的显性负突变体，缺少N端RING和锌指结构域，尽管在人胚胎肾293细胞中也没有抑制IRAK-1诱导的NF-κB活化。 TRAF6突变体强烈抑制了MyD88诱导的激活。不管IRAK-1的表达水平如何，TRAF6的显性负突变体均不影响IRAK-1诱导的激活。相反，TRAF6表达的小干扰RNA沉默抑制了MyD88诱导的和IRAK-1诱导的激活，并且补充TRAF6显性负突变体不能恢复IRAK-1诱导的激活。 IRAK-1而非MyD88的表达诱导了TRAF6的寡聚，并且IRAK-1和TRAF6显性负突变体与TRAF6相关。这些结果表明，TRAF6参与了MyD88诱导和IRAK诱导的NF-κB活化，但机制不同，并暗示TRAF6根据信号使用独特的机制来活化NF-κB。

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