Reactome | CHUK:IKBKB:IKBKG [cytosol]

CHUK:IKBKB:IKBKG [cytosol]

Stable Identifier

R-HSA-168113

Type

Complex

Species

Homo sapiens

Compartment

cytosol

Synonyms

IKKA:IKBKB:IKBKG, IKK complex, Inhibitor of KappaB kinase (IKK) Complex

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General

Co-immunoprecipitation studies and size exclusion chromatography analysis indicate that the high molecular weight (around 700 to 900 kDa) IKK complex is composed of two kinase subunits (IKK1/CHUK/IKBKA and/or IKK2/IKBKB/IKKB) bound to a regulatory gamma subunit (IKBKG/NEMO) (Rothwarf DMet al. 1998; Krappmann D et al. 2000; Miller BS & Zandi E 2001). Variants of the IKK complex containing IKBKA or IKBKB homodimers associated with NEMO may also exist. Crystallographic and quantitative analyses of the binding interactions between N-terminal NEMO and C-terminal IKBKB fragments showed that IKBKB dimers would interact with NEMO dimers resulting in 2:2 stoichiometry (Rushe M et al. 2008). Chemical cross-linking and equilibrium sedimentation analyses of IKBKG (NEMO) suggest a tetrameric oligomerization (dimers of dimers) (Tegethoff S et al. 2003). The tetrameric NEMO could sequester four kinase molecules, yielding an 2xIKBKA:2xIKBKB:4xNEMO stoichiometry (Tegethoff S et al. 2003). The above data suggest that the core IKK complex consists of an IKBKA:IKBKB heterodimer associated with an IKBKG dimer or higher oligomeric assemblies. However, the exact stoichiometry of the IKK complex remains unclear.

Literature References

PubMed ID	Title	Journal	Year
20434986	NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways Cui, J, Zhu, L, Xia, X, Wang, HY, Legras, X, Hong, J, Ji, J, Shen, P, Zheng, S, Chen, ZJ, Wang, RF	Cell	2010
9751060	IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex Rothwarf, DM, Zandi, E, Natoli, G, Karin, M	Nature	1998
10893415	The I kappa B kinase (IKK) complex is tripartite and contains IKK gamma but not IKAP as a regular component Krappmann, D, Hatada, EN, Tegethoff, S, Li, J, Klippel, A, Giese, K, Baeuerle, PA, Scheidereit, C	J. Biol. Chem.	2000