IKBKE

Official Full Name

inhibitor of nuclear factor kappa B kinase subunit epsilon

Organism

Homo sapiens

Gene ID

9641

Background

IKBKE is a noncanonical I-kappa-B (see MIM 164008) kinase (IKK) that is essential for regulating antiviral signaling pathways. IKBKE has also been identified as a breast cancer (MIM 114480) oncogene and is amplified and overexpressed in over 30% of breast carcinomas and breast cancer cell lines (Hutti et al., 2009 [PubMed 19481526]).[supplied by OMIM, Oct 2009]

Synonyms

IKKE; IKKI; IKK-E; IKK-i

Cat.No.	Product Name	Price
CSC-DC007521	Panoply™ Human IKBKE Knockdown Stable Cell Line	Inquiry
CSC-SC007521	Panoply™ Human IKBKE Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD07987Z	Human IKBKE adenoviral particles	Inquiry
LV15305L	human IKBKE (NM_001193322) lentivirus particles	Inquiry
LV15306L	human IKBKE (NM_014002) lentivirus particles	Inquiry
LV15307L	human IKBKE (NM_001193321) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH318017	shRNA set against Mouse IKBKE (NM_019777.3)	Inquiry
SHL170002	shRNA set against Human IKBKE(NM_001193321.1)	Inquiry
SHH318013	shRNA set against Human IKBKE (NM_014002.3)	Inquiry
SHH318021	shRNA set against Rat IKBKE (NM_001108854.1)	Inquiry
SHL169966	shRNA set against Mouse Ikbke(NM_019777.3)	Inquiry
SHL170152	shRNA set against Human IKBKE(NM_001193322.1)	Inquiry
SHW006733	shRNA set against Danio rerio IKBKE (NM_001002751)	Inquiry

Cat.No.	Product Name	Price
CDFL006113	Mouse Ikbke cDNA Clone(NM_019777.3)	Inquiry
CDFR008422	Rat Ikbke cDNA Clone(NM_001108854.1)	Inquiry
MiUTR1H-04859	IKBKE miRNA 3'UTR clone	Inquiry
MiUTR1H-04860	IKBKE miRNA 3'UTR clone	Inquiry
MiUTR1H-04861	IKBKE miRNA 3'UTR clone	Inquiry
MiUTR1M-05959	IKBKE miRNA 3'UTR clone	Inquiry
CDCB168208	Danio rerio IKBKE ORF Clone (NM_001002751)	Inquiry
CDCB185261	Rabbit IKBKE ORF clone (XM_008268504.1)	Inquiry
CDCL120029	Human IKBKE ORF clone (NM_001193321.1)	Inquiry
CDCL120031	Mouse IKBKE ORF clone (NM_001193322.1)	Inquiry
CDCR254360	Mouse Ikbke ORF Clone(NM_019777.3)	Inquiry
CDCR375477	Rat Ikbke ORF Clone(NM_001108854.1)	Inquiry
CDCS409255	Human IKBKE ORF Clone (BC107812)	Inquiry

Detailed Information

The IKBKE gene encodes IKKε (IκB kinase epsilon) and is located on human chromosome 1q32.1. IKKε is a noncanonical member of the IκB kinase (IKK) family, which also includes the canonical IKKα and IKKβ, as well as another noncanonical member, TBK1. Unlike the classical IKK complexes that primarily respond to pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor, IKKε activation is more closely associated with viral infection and oncogenic signaling. IKKε is a serine/threonine protein kinase whose activation depends on specific post-translational modifications. In antiviral innate immunity, it can be recruited by mitochondrial antiviral-signaling protein (MAVS) downstream of RIG-I-like receptors and activated via K63-linked polyubiquitination. IKKε is inducibly expressed in multiple cell types, particularly in immune and epithelial cells, and its expression is significantly upregulated upon interferon stimulation or activation of oncogenic pathways, providing a basis for its functional roles.

Biological Significance

IKBKE/IKKε functions as a critical signaling hub connecting innate immune responses, inflammation, and malignant transformation. In antiviral immunity, IKKε is indispensable. When cytosolic viral RNA sensors such as RIG-I or MDA5 detect viral nucleic acids, IKKε is recruited and activated. Activated IKKε phosphorylates key transcription factors IRF3 and IRF7, promoting their dimerization and nuclear translocation, thereby initiating transcription of type I interferons and interferon-stimulated genes to establish an antiviral state.

Figure 1. The canonical nuclear factor κB activation pathway. (Mitchell S, et al., 2016)

Additionally, IKKε can activate the NF-κB pathway through phosphorylation of IκBα or direct phosphorylation of RelA/p65, enhancing the production of pro-inflammatory cytokines and chemokines and amplifying the immune response. Beyond its physiological role in host defense, IKKε has been identified as an oncogene, particularly in breast cancer. In a subset of breast cancers and other malignancies, IKBKE is amplified or overexpressed. Oncogenic IKKε promotes tumorigenesis by activating the Akt pathway to enhance cell survival, regulating cell cycle proteins to drive proliferation, and establishing a chronic inflammatory tumor microenvironment to support growth and metastasis. Moreover, IKKε can phosphorylate STAT1, influencing the balance between type I and type II interferon responses, which may play a role in tumor immune editing.

Clinical Relevance

The clinical significance of IKBKE/IKKε arises from its potential as a therapeutic target in cancer and its association with inflammatory diseases. In oncology, due to IKKε's aberrant activation and its promotion of tumor cell survival, proliferation, and inflammatory microenvironments, it is an attractive anticancer drug target. Selective IKKε small-molecule inhibitors have been developed to block its kinase activity, thereby interrupting oncogenic signaling pathways, inducing tumor cell apoptosis, and potentially reversing immunosuppressive microenvironments. Several of these inhibitors are in preclinical development and have shown efficacy in breast, ovarian, and other cancer models. Combining IKKε inhibitors with chemotherapy, targeted therapy, or immune checkpoint blockade is a promising therapeutic strategy.

IKKε expression or activity may also serve as a biomarker for predicting patient prognosis and response to specific therapies. In autoimmune and chronic inflammatory diseases, hyperactivation of IKKε can lead to aberrant type I interferon and pro-inflammatory cytokine production, contributing to the pathogenesis of diseases such as systemic lupus erythematosus. Thus, selective inhibition of IKKε could have therapeutic value. However, the high structural and functional similarity between IKKε and TBK1 presents a challenge in designing inhibitors that selectively target IKKε without affecting TBK1-mediated essential functions, such as antiviral immunity. Precise mapping of IKKε signaling in different disease contexts is essential for effective and targeted interventions.

References

Fitzgerald KA, McWhirter SM, Faia KL, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol. 2003;4(5):491–6.
Boehm JS, Zhao JJ, Yao J, et al. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007;129(6):1065–79.
Hutti JE, Porter MA, Cheely AW, et al. Identification of phosphorylation sites required for IKKε activation. J Biol Chem. 2012;287(22):18637–49.
Mitchell S, Vargas J, Hoffmann A. Signaling via the NFκB system. Wiley Interdiscip Rev Syst Biol Med. 2016 May;8(3):227-41.

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