IKBKE (Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Epsilon), also known as IKKε or IKK-Epsilon, is a serine/threonine protein kinase that plays important roles in the innate immune response, inflammatory signaling, and has been implicated in cancer and metabolic diseases[1]. It is one of the IKK family members (IKKα, IKKβ, IKKγ, IKKε, TBK1).
IKBKE is a human gene whose product iKBKE is a non-canonical IKK family member that phosphorylates IκB proteins and activates NF-κB signaling, but also has IκB-independent functions[2]:. Variants in IKBKE have been implicated in Cancer, Inflammation, Neurodegeneration. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
IKBKE is a non-canonical IKK family member that phosphorylates IκB proteins and activates NF-κB signaling, but also has IκB-independent functions[2:1]:
IKBKE shows tissue-specific expression:
In the brain, IKBKE is expressed in microglia and neurons, with increased expression during neuroinflammation.
Kravchenko VV, Mathison JC, Schwamborn K, et al. IKKi/IKKε plays a key role in integrating signals induced by pro-inflammatory stimuli. J Biol Chem. 2003;278(29):26612-26619. https://pubmed.ncbi.nlm.nih.gov/12750372/ ↩︎
Hemmings BA. IKKε: a kinase involved in the innate immune response. Sci STKE. 2007;2007(378):pe9. https://pubmed.ncbi.nlm.nih.gov/17290066/ ↩︎ ↩︎
Fitzgerald KA, McWhirter SM, Faia KL, et al. IKKε and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol. 2003;4(5):491-496. https://pubmed.ncbi.nlm.nih.gov/12692549/ ↩︎
Hershko DD, Robb BW, Luo G, Hasselgren PO. Multiple transcription factors regulating the expression of the gene encoding atrial natriuretic peptide are activated by IKKε in sepsis. Ann Surg. 2004;239(5):678-685. https://pubmed.ncbi.nlm.nih.gov/15082972/ ↩︎