IKKε Protein, Human (Active, sf9, GST)

IKKε, a serine/threonine kinase, assumes a critical role in orchestrating inflammatory responses to viral infection by activating the type I IFN, NF-kappa-B, and STAT signaling pathways. Upon activation of viral RNA sensors, such as RIG-I-like receptors, IKKε associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), specifically IRF3 and IRF7, as well as DDX3X. This activity enables homodimerization and nuclear translocation of IRF3, leading to the transcriptional activation of pro-inflammatory and antiviral genes, including IFNB. To establish an antiviral state, IKBKE forms diverse complexes, recruiting scaffolding molecules like IPS1/MAVS, TANK, AZI2/NAP1, or TBKBP1/SINTBAD, whose composition varies based on the cell type and stimuli. Activated by polyubiquitination in response to TNFA and interleukin-1, IKKε regulates the NF-kappa-B pathway by phosphorylating CYLD, leading to the dissociation and degradation of the inhibitor/NF-kappa-B complex. Furthermore, IKKε is vital for inducing a subset of ISGs with antiviral activity, potentially through STAT1 phosphorylation at 'Ser-708', which also influences the balance between type I and type II IFN responses. Beyond its role in antiviral defense, IKKε protects against DNA damage-induced cell death, and its involvement in chronic, low-grade inflammation in obesity negatively impacts insulin sensitivity. Additionally, IKKε phosphorylates AKT1, contributing to its multifaceted regulatory functions in cellular processes.