Defective IKBKB (IKK2) does not form a complex with IKBKA and IKBKG

Stable Identifier
Reaction [transition]
Homo sapiens
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I kappa B kinase B (IKBKB or IKK beta) is the catalytic subunit of the IKK complex, which also contains kinase IKK1 (IKBKA/IKKalpha) and a regulatory subunit NEMO (IKBKG/IKKgamma). The IKK complex phosphorylates inhibitors of NFkB (IkB) in response to multiple stimuli. The phosphorylation of the IkB proteins triggers their polyubiquitination and subsequent degradation by the 26S proteasome. Free NFkB dimer translocates to the nucleus where it regulates the expression of target genes. Defects in NFkB signaling can affect both innate and adaptive immune-receptor pathways.

Homozygous duplication c.1292dupG in exon 13 of the IKBKB gene results in loss of expression of IKBKB (IKK beta). This mutation was identified in several patients diagnosed with severe combined immunodeficiency (SCID), a rare, potentially fatal, inherited disorderss associated with lack of mature B- and T-lymphocytes (Pannicke U et al. 2013). Patient-derived fibroblasts showed impaired NFkB-mediated responses upon stimulation with toll like receptor (TLR) ligands such as flagellin and lipopolysaccharide (LPS). Degradation of IkB alpha was absent upon TLR5 stimulation by flagellin. In addition, IL6 production was reduced in response to flagellin or lipopolysaccharide (which is specifically recognized by TLR4) (Pannicke U et al. 2013). Patient-derived B cells produced no immunoglobulins upon stimulation with TLR9 antagonist CpG (Pannicke U et al. 2013).

Literature References
PubMed ID Title Journal Year
24369075 Deficiency of innate and acquired immunity caused by an IKBKB mutation

Pannicke, U, Baumann, B, Fuchs, S, Henneke, P, Rensing-Ehl, A, Rizzi, M, Janda, A, Hese, K, Schlesier, M, Holzmann, K, Borte, S, Laux, C, Rump, EM, Rosenberg, A, Zelinski, T, Schrezenmeier, H, Wirth, T, Ehl, S, Schroeder, ML, Schwarz, K

N. Engl. J. Med. 2013
Normal reaction
Functional status

Loss of function of IKBKB Q432Pfs*62 [cytosol]

Name Identifier Synonyms
severe combined immunodeficiency DOID:627 Severe combined immunodeficiency, combined T and B cell inborn immunodeficiency, SCID, Severe combined immunodeficiency disease (disorder), SCID
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