IκB kinase ɛ (IKKɛ): A therapeutic target in inflammation and cancer

The innate immune system forms our first line of defense against invading pathogens and relies for a major part on the activation of two transcription factors, NF-κB and IRF3. Signaling pathways that activate these transcription factors are intertwined at the level of the canonical IκB kinases (IKKα, IKKβ) and non-canonical IKK-related kinases (IKKɛ, TBK1). Recently, significant progress has been made in understanding the function and mechanism of action of IKKɛ in immune signaling. In addition, IKKɛ impacts on cell proliferation and transformation, and is thereby also classified as an oncogene. Studies with IKKɛ knockout mice have illustrated a key role for IKKɛ in inflammatory and metabolic diseases. In this review we will highlight the mechanisms by which IKKɛ impacts on signaling pathways involved in disease development and discuss its potential as a novel therapeutic target.