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Background
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Nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor and an essential mediator of gene expression during activation of immune and inflammatory responses. NF-κB mediates the expression of a great variety of genes in response to extracellular stimuli including IL-1, TNFα, and bacteria product LPS. NF-κB is associated with IκB proteins in the cell cytoplasm, which inhibit NF-κB activity. IκB kinase (IKK), which phosphorylates IκB and mediates IκB degradation and NF-κB activation, was recently identified by several laboratories. IKK is a serine protein kinase, and the IKK complex contains alpha and beta subunits (IKKα, and IKKβ,). IKKα, and IKKβ, interact with each other and both are essential for the NF-κB activation. IKKα, specifically phosphorylates IκB-α, while IKKβ, phosphorylates both IκB-α, and IκB-β,. Another molecule in the IKK complex termed IKKγ (also known as NEMO) interacts with IKKβ, and is required for the activation of IKK complex and NF-κB by LPS, PMA, TNF, and IL-1 stimulation. IKKγ was also shown to bind to RIP and NIK and to mediate TNF-induced NF-κB activation. IKKε is required for the activation of NF-κB by PMA and T cell receptors but not by TNFα, and IL-1. IKKε message is expressed in a variety of tissues and is inducible by TNFα, IL-1, and LPS.
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