NFκB-inducing kinase inhibits NFκB activity specifically in neurons of the CNS

Journal of Neurochemistry
Xianrong MaoSteven W Barger

Abstract

The control of NFκB in CNS neurons appears to differ from that in other cell types. Studies have reported induction of NFκB in neuronal cultures and immunostaining in vivo, but others have consistently detected little or no transcriptional activation by NFκB in brain neurons. To test if neurons lack some component of the signal transduction system for NFκB activation, we transfected cortical neurons with several members of this signaling system along with a luciferase-based NFκB-reporter plasmid; RelA was cotransfected in some conditions. No component of the NFκB pathway was permissive for endogenous NFκB activity, and none stimulated the activity of exogenous RelA. Surprisingly, however, the latter was inhibited by cotransfection of NFκB-inducing kinase (NIK). Fluorescence imaging of RelA indicated that co-expression of NIK sequestered RelA in the cytoplasm, similar to the effect of IκBα. NIK-knockout mice showed elevated expression of an NFκB-reporter construct in neurons in vivo. Cortical neurons cultured from NIK-knockout mice showed elevated expression of an NFκB-reporter transgene. Consistent with data from other cell types, a C-terminal fragment of NIK suppressed RelA activity in astrocytes as well as neurons. Therefore,...Continue Reading

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Citations

Oct 30, 2019·Anti-cancer Agents in Medicinal Chemistry·Meimei Xu, Yan Zhang
Nov 1, 2016·Journal of Neurochemistry·Steven W Barger
Sep 26, 2017·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Paul A ParconW Sue T Griffin
Jun 2, 2020·World Journal of Diabetes·Valerio CaputoRaffaella Cascella

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