Activated TAK1 mediates phosphorylation of the IKK Complex

Stable Identifier
Homo sapiens
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In humans, the IKKs - IkB kinase (IKK) complex serves as the master regulator for the activation of NF-kappa-B by various stimuli. The IKK complex contains two catalytic subunits, IKK alpha and IKK beta associated with a regulatory subunit, NEMO (IKKgamma). The activation of the IKK complex and the NFkB mediated antiviral response are dependent on the phosphorylation of IKK alpha/beta at its activation loop and the ubiquitination of NEMO (Solt et al 2009; Li et al 2002). NEMO ubiquitination by TRAF6 is required for optimal activation of IKKalpha/beta; it is unclear if NEMO subunit undergoes K63-linked or linear ubiquitination.

This basic trimolecular complex is referred to as the IKK complex. Each catalytic IKK subunit has an N-terminal kinase domain and leucine zipper (LZ) motifs, a helix-loop-helix (HLH) and a C-terminal NEMO binding domain (NBD). IKK catalytic subunits are dimerized through their LZ motifs.

IKK beta is the major IKK catalytic subunit for NF-kappa-B activation. Phosphorylation in the activation loop of IKK beta requires Ser177 and Ser181 and thus activates the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation.

RNA-induced liquid phase separation of SARS-CoV-2 nucleocapsid (N) protein serves as a platform to enhance the interaction between TAK1 and IKK complexes promoting NF-kappa-B-dependent inflammatory responses (Wu Y et al. 2021).

Literature References
PubMed ID Title Journal Year
11460167 TAK1 is a ubiquitin-dependent kinase of MKK and IKK

Deng, L, Inoue, J, Akkaraju, GR, Hong, M, Wang, C, Chen, ZJ

Nature 2001
17496917 Ubiquitin-mediated activation of TAK1 and IKK

Xu, M, Adhikari, A, Chen, ZJ

Oncogene 2007
9744859 Tumor necrosis factor receptor-associated factors (TRAFs)--a family of adapter proteins that regulates life and death

Arch, RH, Gedrich, RW, Thompson, CB

Genes Dev 1998
Catalyst Activity

protein serine/threonine kinase activity of Activated TAK complexes [cytosol]

This event is regulated
Orthologous Events
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