IκB kinase β (IKKβ/IKK2/IKBKB)—A key molecule in signaling to the transcription factor NF-κB

IKKβ/IKBKB (IκB kinase beta), also designated as IKK2, was named after its function of phosphorylating IκB molecules, the inhibitors of NF-κB transcription factors. The kinase activity of IKKβ targets two adjacent serine residues of IκB leading to ubiquitination and proteasomal degradation of the inhibitor, followed by release and activation of NF-κB. Many signaling pathways that activate NF-κB converge at the level of IKKβ. Examples of stimuli leading to IKKβ and subsequent NF-κB activation include inflammatory cytokines (IL-1, TNFα), endotoxins (lipopolysaccharide), viral infection and double strand RNA as well as physical signals such as UV-irradiation. Transcription factors of the NF-κB protein family have a great variety of functions in regulating the immune system, cellular differentiation, survival and proliferation. NF-κB is an essential factor in acute as well as chronic inflammation, a pathological state which is either cause or co-factor in a great variety of diseases. Moreover, recent data suggest that many variants of cancer are characterized by elevated constitutive activity of NF-κB, which can act as a survival factor for malignant cells by its predominantly anti-apoptotic function. Given the tight regulation of NF-κB by IκB molecules and the central role of IKKβ in phosphorylation and degradation of the inhibitor, IKKβ is a very promising target for pharmaceutical substances aiming at interfering with NF-κB activation.