Reactome | NEMO subunit of IKK complex binds to activated IRAK1 upon stimulation of TLR7/8 or 9

NEMO subunit of IKK complex binds to activated IRAK1 upon stimulation of TLR7/8 or 9

Stable Identifier

R-HSA-975119

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, endosome membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

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Immune System (Homo sapiens)

- Innate Immune System (Homo sapiens)
  - Toll-like Receptor Cascades (Homo sapiens)
    - Toll Like Receptor 7/8 (TLR7/8) Cascade (Homo sapiens)
      - MyD88 dependent cascade initiated on endosome (Homo sapiens)
        
        TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (Homo sapiens)
        
        IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation (Homo sapiens)
        
        NEMO subunit of IKK complex binds to activated IRAK1 upon stimulation of TLR7/8 or 9 (Homo sapiens)
    - Toll Like Receptor 9 (TLR9) Cascade (Homo sapiens)
      - MyD88 dependent cascade initiated on endosome (Homo sapiens)
        
        TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (Homo sapiens)
        
        IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation (Homo sapiens)
        
        NEMO subunit of IKK complex binds to activated IRAK1 upon stimulation of TLR7/8 or 9 (Homo sapiens)

General

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NEMO subunit of IKK complex binds to activated IRAK1 upon stimulation of TLR7/8 or 9

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NF-kappa-B essential modulator (NEMO, also known as IKKG abbreviated from Inhibitor of nuclear factor kappa-B kinase subunit gamma) is the regulatory subunit of the IKK complex which phosphorylates inhibitors of NF-kappa-B leading to dissociation of the inhibitor/NF-kappa-B complex. NEMO binds to K63-pUb chains (Ea et al. 2006; Wu et al. 2006), linking K63-pUb-hp-IRAK1 with the IKK complex. Models of IL-1R dependent activation of NF-kappaB suggest that the polyubiquitination of both TRAF6 and IRAK1 within a TRAF6:IRAK1 complex and their subsequent interactions with the TAK1 complex and IKK complex respectively brings these complexes into proximity, facilitating the TAK1-catalyzed activation of IKK (Moynagh, 2008).

Literature References

PubMed ID	Title	Journal	Year
18347055	Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation Conze, DB, Wu, CJ, Thomas, JA, Landstrom, A, Ashwell, JD	Mol Cell Biol	2008
16547522	Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected] Wu, CJ, Conze, DB, Li, T, Srinivasula, SM, Ashwell, JD	Nat Cell Biol	2006
18180283	Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase Windheim, M, Stafford, M, Peggie, M, Cohen, P	Mol Cell Biol	2008