IFIT5 positively regulates NF-κB signaling through synergizing the recruitment of IκB kinase (IKK) to TGF-β-activated kinase 1 (TAK1)

Cellular Signalling
Caishang ZhengHanzhong Wang

Abstract

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.

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Citations

Sep 21, 2018·The Journal of General Virology·Harriet V Mears, Trevor R Sweeney
Sep 30, 2016·Journal of Virology·Zhangtao JiangChunfu Zheng
May 2, 2019·Frontiers in Immunology·Veronica ChicoMaria Del Mar Ortega-Villaizan
Jan 11, 2020·Frontiers in Molecular Biosciences·Vijaya Kumar PiduguTe-Chang Lee
Jul 10, 2020·Veterinary Research·Ning LiSidang Liu
Apr 17, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Na ZhangGuangliang Liu
Jul 16, 2021·The Journal of Biological Chemistry·Matthea R SandersonRachel Wevrick

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