Beyond NF-κB activation: nuclear functions of IκB kinase α

I kappa B kinase (IKK) complex, the master kinase for NF-kappa B activation, contains two kinase subunits, IKK alpha and IKK beta. In addition to mediating NF-kappa B signaling by phosphorylating I kappa B proteins during inflammatory and immune responses, the activation of the IKK complex also responds to various stimuli to regulate diverse functions independently of NF-kappa B. Although these two kinases share structural and biochemical similarities, different sub-cellular localization and phosphorylation targets between IKK alpha and IKK beta account for their distinct physiological and pathological roles. While IKK beta is predominantly cytoplasmic, IKK alpha has been found to shuttle between the cytoplasm and the nucleus. The nuclear-specific roles of IKK alpha have brought increasing complexity to its biological function. This review highlights major advances in the studies of the nuclear functions of IKK alpha and the mechanisms of IKK alpha nuclear translocation. Understanding the nuclear activity is essential for targeting IKK alpha for therapeutics.