RACK1 modulates NF-κB activation by interfering with the interaction between TRAF2 and the IKK complex
RACK1 modulates NF-κB activation by interfering with the interaction between TRAF2 and the IKK complex
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RACK1 通过干扰 TRAF2 和 IKK 复合物之间的相互作用来调节 NF-kappa B 激活
DOI：
10.1038/cr.2013.162
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发表时间：
2014-03-01
期刊：
影响因子：
44.1
通讯作者：
Xie, Dong
中科院分区：
文献类型：
--
作者：
Yao, Fan;Long, Ling-Yun;Xie, Dong
转录因子NF-kappa B在天然免疫应答多种刺激中起着关键作用，该途径的协调调控决定了宿主对细胞外信号的适当应答。在本研究中，我们发现RACK1是一种新的负调控因子，参与了核因子-kappaB信号转导、核因子-kappaB介导的细胞因子诱导和炎症反应。RACK1以肿瘤坏死因子触发的方式与IKK复合体发生物理结合。这种相互作用干扰了IKK复合体向TRAF2的募集，而TRAF2是IKK磷酸化和随后由肿瘤坏死因子激活的关键步骤。RACK1通过调节TRAF2和IKK之间的相互作用，调节核因子-kappaB的激活水平，以响应不同强度的刺激。我们的研究结果表明，RACK1通过调节IKK的激活，在控制肿瘤坏死因子-kappaB信号的敏感性中发挥重要作用，并为炎症反应的负性调控提供了新的视角。
The transcription factor NF-kappa B plays a pivotal role in innate immunity in response to a variety of stimuli, and the coordinated regulation of this pathway determines the proper host responses to extracellular signals. In this study, we identified RACK1 as a novel negative regulator of NF-kappa B signaling, NF-.B-mediated cytokine induction and inflammatory reactions. RACK1 physically associates with the IKK complex in a TNF-triggered manner. This interaction interferes with the recruitment of the IKK complex to TRAF2, which is a critical step for IKK phosphorylation and subsequent activation triggered by TNF. By modulating the interaction between TRAF2 and IKK, RACK1 regulates the levels of NF-kappa B activation in response to different intensities of stimuli. Our findings suggest that RACK1 plays an important role in controlling the sensitivity of TNF-triggered NF-kappa B signaling by regulating IKK activation and provide new insight into the negative regulation of inflammatory reactions.