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

Xianrong Mao, Bounleut Phanavanh, Hamdan Hamdan, Andréa M. Moerman-Herzog, Steven W. Barger

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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, the inhibitory ability of the NIK C-terminus was unbiased with regard to cell type. However, inhibition of NFκB by full-length NIK is a novel outcome that appears to be specific to CNS neurons. This has implications for unique aspects of transcription in the CNS, perhaps relevant to aspects of development, neuroplasticity, and neuroinflammation.

Original languageBritish English
Pages (from-to)154-163
Number of pages10
JournalJournal of Neurochemistry
Issue number2
StatePublished - Apr 2016


  • luciferase
  • MAP3K14
  • NFκB
  • RelA
  • transcription
  • β-galactosidase


Dive into the research topics of 'NFκB-inducing kinase inhibits NFκB activity specifically in neurons of the CNS'. Together they form a unique fingerprint.

Cite this