IKKε (IKBKE) is ubiquitinated within the activated TLR3 complex

Stable Identifier
R-HSA-9830710
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Influenza A virus, Rotavirus, Hepatitis B virus, Hepatitis C Virus, Human herpesvirus 1
Compartment
endosome membrane, cytosol
Synonyms
IKBKE is ubiquitinated within IKBKE:K63pUb-TANK:K63pUb-TRAF3:TICAM1:TLR3:viral
ReviewStatus
5/5
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IKKε (IKBKE) is ubiquitinated within the activated TLR3 complex
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Pathogen-associated inflammatory signaling pathways result in activation of inhibitor of kappaB kinase epsilon (IKKε, IKBKE) and its close homolog TANK-binding kinase 1 (TBK1). Activated TBK1 and IKKε (IKBKE) induce type I interferon production and modulate nuclear factor kappa-B (NF-kappa-B) signaling (Fitzgerald KA et al., 2003; Hemmi H et al., 2004; Gatot JS et al., 2007). Both TBK1 and IKKε (IKBKE) are regulated by K63-linked polyubiquitination on lysines 30 (K30) and 401 (K401) (Tu D et al., 2013; Zhou AY et al., 2013). Structural studies of TBK1 reveal a dimeric assembly which is mediated by several interfaces involving an N-terminal kinase domain (KD), a ubiquitin-like domain (ULD), and an alpha-helical scaffold dimerization domain (SDD) of TBK1 (Larabi A et al., 2013; Tu D et al., 2013). The ULD of TBK1 (and IKKε) is involved in the control of kinase activation, substrate presentation and downstream signaling (Ikeda F et al., 2007; Tu D et al., 2013). Ubiquitination of TBK1 rearranges the N-terminal KD into an active conformation while maintaining the overall dimer conformation (Larabi A et al., 2013). Although dimerization of IKKε (IKBKE) has not been demonstrated experimentally, the ubiquitination sites and dimer contacts are conserved in IKKε suggesting that TBK1 and IKKε are regulated through similar activation mechanisms (Tu D et al., 2013; Zhou AY et al., 2013).

This Reactome event shows ubiquitination of IKKε (IKBKE) at K30 and K401 within the activated TLR3 complex.

Literature References
PubMed ID Title Journal Year
17599067 Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes

Ikeda, F, Hecker, CM, Rozenknop, A, Nordmeier, RD, Rogov, V, Hofmann, K, Akira, S, Dötsch, V, Dikic, I

EMBO J 2007
23453969 IKKε-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex

Zhou, AY, Shen, RR, Kim, E, Lock, YJ, Xu, M, Chen, ZJ, Hahn, WC

Cell Rep 2013
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Authored
Shamovsky, V  (2023-02-10)
Reviewed
Munitić, I  (2024-02-28)
Franjkić, T  (2024-02-28)
Created
Shamovsky, V  (2023-03-13)
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