IKKα 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. IKKα is an essential regulator of NF-kappa-B-dependent gene expression through control of promoter-associated histone phosphorylation after cytokine exposure. IKKα is a critical component of the cytoplasmic transductional-transcriptional processor leading to induction of IFNα production. IKKα is also involved in the epidermis where it antagonizes mitogenic and angiogenic signals and represses tumor progression and metastases.
The Toll-like receptor (TLR) family has important roles in microbial recognition and dendritic cell activation. TLRs 7 and 9 can recognize nucleic acids and trigger signalling cascades that activate plasmacytoid dendritic cells to produce interferon-alpha (IFN-alpha) (refs 7, 8). TLR7/9-mediated
Stimulation of TNFR1 by TNFα can promote three distinct alternative mechanisms of cell death: necroptosis, RIPK1-independent and -dependent apoptosis. How cells decide which way to die is unclear. Here, we report that TNFα-induced phosphorylation of RIPK1 in the intermediate domain
NF-kappaB is a principal transcriptional regulator of diverse cytokine-mediated processes and is tightly controlled by the IkappaB kinase complex (IKK-alpha/beta/gamma). IKK-beta and IKK-gamma are critical for cytokine-induced NF-kappaB function, whereas IKK-alpha is thought to be involved in other regulatory pathways.
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