TBK1/IKK epsilon complex interacts with MAVS bound TRAF3

Stable Identifier
R-HSA-918225
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Influenza A virus, Human respiratory syncytial virus A, Rotavirus, Hepatitis C Virus, Measles virus, Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol, mitochondrial outer membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
TBK1/IKK epsilon complex interacts with MAVS bound TRAF3
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
TRAF3 binds both mitochondrial antiviral-signaling protein (MAVS, also known as IPS‑1) and downstream interferon regulatory factor 3/7 (IRF3/7) kinases TBK1 and IKK‑epsilon (IKKi, IKBKE) and thus serves as a critical link between RIG‑I (DDX58)/MDA5 (IFIH1) adaptors and downstream regulatory kinases important for interferon regulatory factor (IRF) activation (Oganesyan et al. 2006).

SIKE (Suppressor of IKK-epsilon) interacts with IKBKE and TBK1. SIKE is associated with TBK1 under physiological conditions and dissociated from TBK1 upon viral infection. Overexpression of SIKE disrupted the interactions of IKBKE or TBK1 with RIG‑I (DDX58).

SARS-CoV-1 M protein prevents the formation of the TRAF3:TANK:TBK1/IKBKE complex and thereby inhibits TBK1/IKBKE-dependent activation of IRF3/IRF7 transcription factors (Siu KL et al. 2009).

Literature References
PubMed ID Title Journal Year
16281057 SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways

Liu, T, Chen, D, Xu, LG, Shu, HB, Zhai, Z, Huang, J

EMBO J 2005
16306936 Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response

Perry, A, Saha, SK, Oganesyan, G, He, JQ, Guo, B, Shahangian, A, Cheng, G, Zarnegar, B

Nature 2006
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
M:TBK1 [endoplasmic reticulum-Golgi intermediate compartment membrane] (Homo sapiens)
Active Unit
M [endoplasmic reticulum-Golgi intermediate compartment membrane]
Orthologous Events
TBK1/IKK epsilon bind to TANK:TRAF3/TRAF6 complex followed by their activation (Gallus gallus)
Authored
Garapati, P V  (2010-08-02)
Reviewed
Messina, F  (2022-02-18)
Akira, S  (2010-10-30)
Kawai, T  (2010-10-30)
Created
Garapati, P V  (2010-08-02)
Cite Us!