Reactome | TANK binds K63-poly-Ub-TRAF3:TICAM1:activated TLR4

TANK binds K63-poly-Ub-TRAF3:TICAM1:activated TLR4

Stable Identifier

R-HSA-5362486

Type

Reaction [binding]

Species

Homo sapiens

Compartment

endosome membrane, cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

Immune System (Homo sapiens)

- Innate Immune System (Homo sapiens)
  - Toll-like Receptor Cascades (Homo sapiens)
    - Toll Like Receptor 4 (TLR4) Cascade (Homo sapiens)
      - MyD88-independent TLR4 cascade (Homo sapiens)
        
        TRIF (TICAM1)-mediated TLR4 signaling (Homo sapiens)
        
        Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) (Homo sapiens)
        
        TANK binds K63-poly-Ub-TRAF3:TICAM1:activated TLR4 (Homo sapiens)

General

SBML | | PDF

SVG | | PPTX | SBGN

TANK binds K63-poly-Ub-TRAF3:TICAM1:activated TLR4

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

TRAF family member-associated NF-kB activator (TANK or ITRAF) is a TRAF-binding protein that has been implicated in RLR, TNFR and IL-1R/TLR signaling pathways in mammals (Rothe M et a.l 1996; Pomerantz JL and Baltimore D 1999; Li C et al. 2002; Guo B and Cheng G 2007; Konno H 2009). TANK was shown to interact with TBK1, IKK epsilon, IPS-1, TRIF (TICAM1), IRF3 and is thought to be a part of the TRAF3-containing complex (Pomerantz JL and Baltimore D 1999; Guo B and Cheng G 2007; Gatot JC et al. 2007). Upon microbe stimulation TANK is believed to induce IRF-dependent type I IFN production in mammalian cells by linking kinase TBK1 or IKK epsilon with upstream mediators TRAF3/6 (Guo B and Cheng G 2007; Gatot JC et al. 2007). In addition, TANK is thought to act synergistically with IKK epsilon or TBK1 to link them to IKK complex via interaction with NEMO (IKK gamma), where TBK1/IKK epsilon may modulate NFkB activation (Chariot A et al. 2002). TANK influence on NFkB activation was found to occur via either positive or negative regulation (Guo B and Cheng G 2007, Konno H et al. 2009; Pomerantz JL and Baltimore D 1999; Kawagoe T et al. 2009).

Two other adaptor proteins NAK-associated protein 1 (NAP1) and SINTBAD (not shown here) have been implicated in TBK1/IKKepsilon-mediated activation of IRF3 (Sasai M et al. 2005; Ryzhakov G and Randow F 2007). Structural and functional studies showed that TANK, NAP1 and SINTBAD share a common region which mediates association with the coiled-coil 2 in TBK1 (Ryzhakov G and Randow F 2007; Goncalves A et al. 2011; Larabi A et al. 2013; Tu D et al. 2013). TANK, NAP1 and SINTBAD were found to compete for TBK1 binding (Ryzhakov G and Randow F 2007; Goncalves A et al. 2011), TBK1 is thought to form alternative complexes with each adaptor TANK, NAP1 or SINTBAD, rather than a single large multiprotein complex containing all three adaptors (Goncalves A et al. 2011; Larabi A et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
17823124	Lipopolysaccharide-mediated interferon regulatory factor activation involves TBK1-IKKepsilon-dependent Lys(63)-linked polyubiquitination and phosphorylation of TANK/I-TRAF Muraille, E, Close, P, Brown, K, Siebenlist, U, Chau, TL, Chapelle, JP, Piette, J, Warnier, M, Gatot, JS, Patrascu, F, Dejardin, E, Chariot, A, Gioia, R	J. Biol. Chem.	2007
17047224	Regulation and function of IKK and IKK-related kinases Karin, M, Hacker, H	Sci STKE	2006