Overview:

IKKbeta is a serine/threonine protein kinase that phosphorylates the I-kappa-B protein which is an inhibitor of the transcription factor NF-kappa-B complex. Phosphorylation of I-kappa-B protein triggers the degradation of the inhibitor via the ubiquitination pathway, thereby activating NF-kappa-B complex. The activity of IKKbeta is stimulated by TNF and IL1 and IKKbeta forms a heterodimer that interacts with NIK (1). Overexpression of catalytically inactive IKKbeta blocks cytokine-induced NF-kappa-B activation. Aspirin and sodium salicylate can specifically inhibit IKKbeta activity in vitro and in vivo by binding to IKKbeta to reduce ATP binding (2).

References:

1. Woronicz, J D. et al: IkappaB kinase-beta: NF-kappa-B activation and complex formation with IkappaB kinase-alpha and NIK. Science 278: 866-869, 1997.

2. Yin, M.-J. et al: The anti-inflammatory agents aspirin and salicylate inhibit the activity of I-kappa-B kinase-beta. Nature 396: 77-80, 1998.