IKBKE
IKBKE (inhibitor of nuclear factor kappa B kinase subunit epsilon, also IKKE, IKK-i or KIAA0151) is a noncanonical I-kappa-B kinase and serine/threonine kinase. It regulates antiviral and inflammatory signalling through type I interferon, NF-kappa-B and STAT pathways. Browse Assay Genie's current range of IKBKE research reagents below, or read on for the biology behind the target.
IKBKE is a serine/threonine kinase with an essential role in regulating inflammatory responses to viral infection. After activation of viral RNA sensors such as RIG-I-like receptors, it associates with DDX3X and phosphorylates the interferon regulatory factors IRF3 and IRF7, as well as DDX3X. This allows IRF3 to homodimerise and move into the nucleus, where it drives transcription of pro-inflammatory and antiviral genes including IFNB. The composition of IKBKE-containing complexes depends on cell type and stimulus, and scaffolding molecules such as IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to them.
IKBKE is also required for induction of a subset of interferon-stimulated genes, possibly through phosphorylation of STAT1 at Ser-708. This modification appears to favour assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) over GAF (STAT1:STAT1) complexes, so tuning the balance between type I and type II interferon responses. In NF-kappa-B signalling, IKBKE is activated by polyubiquitination in response to TNFA and interleukin-1. It phosphorylates CYLD, NFKBIA and p65/RELA, and also phosphorylates and activates STING1. Phosphorylation of NFKBIA leads to dissociation of the inhibitor from NF-kappa-B and its degradation. Further reported roles include protecting cells against DNA damage-induced cell death, phosphorylating AKT1, and sustaining the chronic, low-grade inflammation of obesity that harms insulin sensitivity.
The IKBKE gene belongs to the I kappa B kinase family and the protein sits in the I-kappa-B kinase subfamily of the Ser/Thr protein kinase superfamily. The protein localises to the cytoplasm and nucleus, including PML bodies. It was previously named inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon. IKBKE has also been identified as a breast cancer oncogene, amplified and overexpressed in over 30% of breast carcinomas and breast cancer cell lines. The mouse ortholog is Ikbke.
IKBKE phosphorylates IRF3 and IRF7 downstream of viral RNA sensors, making it central to type I interferon induction and antiviral gene expression.
Activated by TNFA and interleukin-1, IKBKE phosphorylates CYLD, NFKBIA and p65/RELA, making it a useful node for studying inflammatory signalling.
IKBKE is a recognised breast cancer oncogene, amplified and overexpressed in over 30% of breast carcinomas and cell lines.
IKBKE sustains chronic, low-grade inflammation in obesity, which impairs insulin sensitivity, linking innate immune kinases to energy balance.
IKBKE is a serine/threonine kinase that regulates antiviral and inflammatory responses. It phosphorylates IRF3, IRF7, STAT1, CYLD, NFKBIA and p65/RELA, so activating type I interferon, STAT and NF-kappa-B signalling. It also protects cells against DNA damage-induced cell death.
IKBKE is also called IKKE, IKK-i and KIAA0151. Its earlier HGNC name was inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon. It is described as a noncanonical I-kappa-B kinase and belongs to the I-kappa-B kinase subfamily.
IKBKE has been identified as a breast cancer oncogene, amplified and overexpressed in over 30% of breast carcinomas and cell lines. It is also linked to obesity-related inflammation. The mouse ortholog is Ikbke; check the datasheet of any product for its validated reactivity.
Other I-kappa-B kinase family members, interferon regulatory factors and NF-kappa-B pathway proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q14164; product specifications from Assay Genie datasheets.