TBK1 is ubiquitinated within TBK1:K63polyUb-TANK:K63polyUb-TRAF3:TRIF:activated TLR3

Stable Identifier
R-HSA-9828200
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
TBK1 is ubiquitinated within the activated TLR3 complex
ReviewStatus
5/5
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TBK1 is ubiquitinated within TBK1:K63polyUb-TANK:K63polyUb-TRAF3:TRIF:activated TLR3
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Pathogen‑associated inflammatory signaling pathways result in activation of TANK‑binding kinase 1 (TBK1) and its close homolog inhibitor of kappaB kinase epsilon (IKKε , IKBKE). 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; Taft J et al., 2021; Wegner J et al., 2023). Structural studies of TBK1 reveal a dimeric assembly that is mediated by several interfaces involving an N-terminal kinase domain (KD), an 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 IKBKE) is involved in the control of kinase activation, substrate presentation, and downstream signaling (Ikeda F et al., 2007; Tu D et al., 2013). TBK1 dimer is a subject to K63‑linked polyubiquitination on lysines 30 (K30) and 401 (K401) (Tu D et al., 2013). Activation of TBK1 rearranges the N-terminal KD into an active conformation while maintaining the overall dimer conformation (Larabi A et al., 2013). The E3 Ub ligase(s) that catalyze this reaction in response to various stimuli are reviewed by Runde AP et al. (2022).

This Reactome reaction shows the ubiquitination of TBK1 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
23453971 Crystal structure and mechanism of activation of TANK-binding kinase 1

Larabi, A, Devos, JM, Ng, SL, Nanao, MH, Round, A, Maniatis, T, Panne, D

Cell Rep 2013
23453972 Structure and ubiquitination-dependent activation of TANK-binding kinase 1

Tu, D, Zhu, Z, Zhou, AY, Yun, CH, Lee, KE, Toms, AV, Li, Y, Dunn, GP, Chan, E, Thai, T, Yang, S, Ficarro, SB, Marto, JA, Jeon, H, Hahn, WC, Barbie, DA, Eck, MJ

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