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首页> 外文期刊>Molecular and Cellular Biology >The p65/RelA Subunit of NF-κB Suppresses the Sustained, Antiapoptotic Activity of Jun Kinase Induced by Tumor Necrosis Factor
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The p65/RelA Subunit of NF-κB Suppresses the Sustained, Antiapoptotic Activity of Jun Kinase Induced by Tumor Necrosis Factor

机译：NF-κB的p65 / RelA亚基抑制肿瘤坏死因子诱导的Jun激酶的持续抗凋亡活性

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摘要

Tumor necrosis factor (TNF) signaling through the TNF receptors involves the recruitment of key signaling factors, leading to the activation of both the transcription factor NF-κB and the stress-activated Jun kinase (JNK). In most cells, TNF signaling leads to a rapid and transient increase in JNK activity. However, we show that TNF treatment leads to the sustained activation of JNK in cells that are null for the p65/RelA subunit of NF-κB as well as in cells expressing the super-repressor form of IκB. In addition, the data indicate that the ability of p65/RelA to regulate gene expression is required to suppress the persistent activation of JNK. Interestingly, this suppression occurs upstream of JNK, within the signal transduction cascade leading to JNK activation, without affecting the stress-activated kinase p38. Since NF-κB has previously been shown to be involved in the suppression of TNF-induced apoptosis, we were interested in determining the role of deregulated JNK activity, induced by the loss of NF-κB, in controlling the cell death response. Through the use of different approaches for inhibition of JNK, we show that the suppression of JNK activity in cells that lack active NF-κB enhances the apoptotic response to TNF. These data suggest that the activity of JNK in cells blocked for NF-κB function provides an antiapoptotic signal and explains, at least partly, why a significant number of NF-κB null cells remain viable following TNF treatment.
机译：通过TNF受体的肿瘤坏死因子（TNF）信号涉及关键信号因子的募集，从而导致转录因子NF-κB和应激激活的Jun激酶（JNK）均被激活。在大多数细胞中，TNF信号传导会导致JNK活性迅速而短暂地增加。但是，我们显示，TNF处理导致NF-κB的p65 / RelA亚基无效的细胞以及表达IκB的超阻遏物的细胞中JNK的持续活化。另外，数据表明p65 / RelA调节基因表达的能力是抑制JNK持续激活所必需的。有趣的是，这种抑制作用发生在导致JNK激活的信号转导级联中JNK的上游，而不影响应力激活的激酶p38。由于以前已证明NF-κB参与了TNF诱导的细胞凋亡的抑制，因此我们有兴趣确定由NF-κB的丧失引起的JNK活性失调在控制细胞死亡反应中的作用。通过使用不同的抑制JNK的方法，我们表明在缺乏活性NF-κB的细胞中抑制JNK活性可增强对TNF的凋亡反应。这些数据表明，在被NF-κB功能阻断的细胞中JNK的活性提供了抗凋亡信号，并至少部分解释了为什么TNF治疗后仍有大量的NF-κB无效细胞存活。

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