Abstract
The transcription factor NF-кB is kept inactive in the cytoplasm by interaction with the inhibitory molecule IкB. In response to multiple stimuli, such as inflammatory cytokines, bacterial lipopolysaccharide (LPS), viral infection or stress, IкB is phosphorylated on two critical serine residues. This modification allows its recognition and destruction via the proteasome degradation machinery. As a consequence, free NF-кB enters the nucleus and activates transcription of a variety of genes participating in immune and inflammatory response, cell adhesion, growth control or protection against apoptosis (Karin & Ben-Neriah, 2000). For many years, the kinase that phosphorylates IкB (IKK) has remained elusive. Upon biochemical fractionation, it has finally been identified as a high-molecular mass complex migrating around 700–900 kDa and containing two related catalytic subunits, viz. IKK-1 (or IKKα) and IKK-2 (or IKKβ) (Israël, 2000). An additional component, NEMO/IKKγ, has been subsequently identified by genetic complementation of an NF-кB activation-defective cell line (Yamaoka et al., 1998) and sequencing of IKK-associated polypeptides (Rothwarf et al., 1998; Mercurio et al., 1999). In contrast to IKK-1 and IKK-2, NEMO/IKKγ exhibits no catalytic properties, but acts as a regulatory subunit of IKK. Cell lines defective for NEMO/IKKγ do not activate NF-кB in response to many stimuli, demonstrating the key role of this protein in activating the NF-кB pathway. The NEMO/IKKγ gene is located on chromosome X at Xq28 (Jin & Jeang, 1999).
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Courtois, G., Israël, A. (2003). NF-кB in Genetic Disorders. In: Beyaert, R. (eds) Nuclear Factor кB. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0163-2_14
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DOI: https://doi.org/10.1007/978-94-010-0163-2_14
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