Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) (IKBKE)

Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE), also known as IKK-epsilon or IKK-i, is a non-canonical member of the I-kappa-B kinase family that serves as a critical regulator of innate immunity and inflammatory signaling (UniProt Q9UQL6; NCBI Gene 9641). It primarily functions by phosphorylating interferon regulatory factors (IRF3 and IRF7) and the NF-kappaB inhibitor I-kappa-B alpha, thereby inducing the expression of Type I interferons and pro-survival genes (Boehm et al., 2007, PMID: 17548596). IKBKE is recognized as a potent oncogene, frequently overexpressed or amplified (often via the 1q32 locus) in breast, ovarian, and pancreatic cancers, where it drives cell proliferation and epithelial-to-mesenchymal transition (Barbie et al., 2009, PMID: 19847263). Beyond oncology, IKBKE plays a significant role in metabolic diseases; its expression is induced by high-fat diets, and its inhibition has been shown to improve insulin sensitivity and reduce inflammation in obesity models (Reilly et al., 2013, PMID: 23396106). Pharmacological targeting of IKBKE involves small molecule inhibitors like Amlexanox, which compete for the ATP-binding site of the kinase domain to suppress its downstream signaling effects (PubChem CID 2161). While primarily targeted at the protein level, the IKBKE mRNA transcript itself serves as a biomarker for gene amplification and a potential substrate for future RNA-interference-based therapeutic strategies.

Other names

IKK-epsilonIKK-iIKKIInhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilonKIAA0151

Inhibition of serine/threonine kinase activity, specifically blocking the phosphorylation of IRF3 and I-kappa-B to modulate inflammatory and pro-survival signaling pathways.