IFIT5 positively regulates NF-kappaB signaling through synergizing the recruitment of IkappaB kinase (IKK) to TGF-beta-activated kinase 1 (TAK1).
IFIT5 positively regulates NF-kappaB signaling through synergizing the recruitment of IkappaB kinase (IKK) to TGF-beta-activated kinase 1 (TAK1).
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IFIT5 通过协同 IkappaB 激酶 (IKK) 与 TGF-β 激活激酶 1 (TAK1) 的募集来正向调节 NF-kappaB 信号传导。
DOI：
10.1016/j.cellsig.2015.08.018
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Wang Hanzhong
中科院分区：
文献类型：
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作者：
Zheng Caishang;Zheng Zhenhua;Zhang Zhenfeng;Meng Jin;Liu Yan;Ke Xianliang;Hu Qinxue;Wang Hanzhong
NF-κB信号通路的精确调控对有效的宿主免疫应答至关重要。然而，不同刺激物激活NF-κB的具体分子机制尚未完全清楚。IFIT 5是干扰素诱导的三肽重复序列家族成员之一，它通过与TAK 1和IKK相互作用，增强IKK磷酸化和NF-κB活化。TNF-α处理后，IFIT 5与TAK 1或IKK复合物相互作用，并以剂量依赖性方式协同IKK向TAK 1的募集。与这些观察结果一致，IFIT 5的敲低减少了IKK向TAK 1的募集，并显著减弱了IKK磷酸化，进一步减少了NF-κB靶基因IL-8和ICAM-1的产生。此外，我们发现IFIT 5还通过调节IKK向TAK 1的募集，促进SeV诱导的IKK磷酸化和NF-κB活化。我们的研究结果确定了IFIT 5作为IKK磷酸化和NF-κB激活的正调节因子的先前未被认识的作用，强调IFIT 5作为先天免疫的重要介质。
Precise regulation of NF-κB signaling pathways is essential to effective host immune response. However, the specific molecular mechanism underlying NF-κB activation by different stimuli is not fully understood. Here we demonstrate that IFIT5, one of the interferon induced tetratricopeptide repeat family members, enhances IKK phosphorylation and NF-κB activation through interacting with TAK1 and IKK. Following TNF-α treatment, IFIT5 interacted with TAK1 or IKK complex and synergized the recruitment of IKK to TAK1 in a dose dependent manner. Consistent with these observations, knockdown of IFIT5 decreased the recruitment of IKK to TAK1 and markedly weakened IKK phosphorylation, further reducing the production of NF-κB target genes IL-8 and ICAM-1. Moreover, we found that IFIT5 also promoted SeV-induced IKK phosphorylation and NF-κB activation by regulating the recruitment of IKK to TAK1. Our findings identify a previously unrecognized role of IFIT5 as a positive regulator in IKK phosphorylation and NF-κB activation, highlighting that IFIT5 serves as an important mediator in innate immunity.