IκB kinase β (1KKβ/1KK2/1KBKB) -: A key molecule in signaling to the transcription factor NF-κB

IKK beta/IKBKB (I kappa B kinase beta), also designated as IKK2, was named after its function of phosphorylating I kappa B molecules, the inhibitors of NF-kappa B transcription factors. The kinase activity of IKK beta targets two adjacent serine residues of I kappa B leading to ubiquitination and proteasomal degradation of the inhibitor, followed by release and activation of NF-kappa B. Many signaling pathways that activate NF-kappa B converge at the level of IKK beta. Examples of stimuli leading to IKK beta and subsequent NF-kappa B activation include inflammatory cytokines (IL- 1, TNF alpha), endotoxins (lipopolysaccharide), viral infection and double strand RNA as well as physical signals such as UV-irradiation. Transcription factors of the NF-kappa BK protein family have a great variety of functions in regulating the immune system, cellular differentiation, survival and proliferation. NF-kappa B 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-kappa B, which can act as a survival factor for malignant cells by its predominantly anti-apoptotic function. Given the tight regulation of NF-kappa B by I kappa B molecules and the central role of IKK beta in phosphorylation and degradation of the inhibitor, IKK beta is a very promising target for pharmaceutical substances aiming at interfering with NF-kappa BK activation. (C) 2008 Elsevier Ltd. All rights reserved.