Overview:
IKKalpha 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 (1). IKKalpha is an essential regulator of NF-kappa-B-dependent gene expression through control of promoter-associated histone phosphorylation after cytokine exposure (2). IKKalpha is a critical component of the cytoplasmic transductional-transcriptional processor leading to induction of IFNalpha production. IKKalpha is also involved in the epidermis where it antagonizes mitogenic and angiogenic signals and represses tumor progression and metastases.
References:
1. Anest, V.et.al: A nucleosomal function for I-kappa-B kinase-alpha in NF-kappa-B-dependent gene expression. Nature 423: 659-663, 2003.2. Hoshino, K. et.al: I-kappa-B kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9. Nature 440: 949-953, 2006.
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