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NF-kappa-B inhibitor binds NF-kappa-B complex
Stable Identifier
R-HSA-9630923
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
Immune System (Homo sapiens)
Cytokine Signaling in Immune system (Homo sapiens)
Signaling by Interleukins (Homo sapiens)
Interleukin-1 family signaling (Homo sapiens)
Interleukin-1 signaling (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (Homo sapiens)
Innate Immune System (Homo sapiens)
Toll-like Receptor Cascades (Homo sapiens)
Toll Like Receptor 10 (TLR10) Cascade (Homo sapiens)
MyD88 cascade initiated on plasma membrane (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (Homo sapiens)
Toll Like Receptor 2 (TLR2) Cascade (Homo sapiens)
Toll Like Receptor TLR1:TLR2 Cascade (Homo sapiens)
MyD88:MAL(TIRAP) cascade initiated on plasma membrane (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (Homo sapiens)
Toll Like Receptor TLR6:TLR2 Cascade (Homo sapiens)
MyD88:MAL(TIRAP) cascade initiated on plasma membrane (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (Homo sapiens)
Toll Like Receptor 3 (TLR3) Cascade (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (Homo sapiens)
Toll Like Receptor 4 (TLR4) Cascade (Homo sapiens)
MyD88-independent TLR4 cascade (Homo sapiens)
TRIF (TICAM1)-mediated TLR4 signaling (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (Homo sapiens)
MyD88:MAL(TIRAP) cascade initiated on plasma membrane (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (Homo sapiens)
Toll Like Receptor 5 (TLR5) Cascade (Homo sapiens)
MyD88 cascade initiated on plasma membrane (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (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)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (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)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B inhibitor binds NF-kappa-B complex (Homo sapiens)
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NF-kappa-B is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins, called NF-kappa-B inhibitors (IkBs, NFKBIA or NFKBIB). IkBs proteins such as NFKBIA, NFKBIB or NFKBIE are characterized by the presence of six to seven ankyrin repeat motifs, which mediate interaction with the Rel homology domain (RHD). RHD mediates DNA binding, dimerization and nuclear localization (Jacobs MD & Harrison SC 1998; Manavalan B et al. 2010). NF-kappa-B inhibitors (IkBs) mask the nuclear localization signal (NLS) of the NF-kappa-B p65 subunit (ReLA, p65) preventing the nuclear translocation of NF-kappa-B (Jacobs MD & Harrison SC 1998; Cervantes CF et al. 2011). A key event in NF-kappa-B activation involves phosphorylation of IkB (at sites equivalent to Ser32 and Ser36 of NFKBIA (IkB-alpha) or Ser19 and Ser22 of NFKBIB (IkB-beta) by the IκB kinase (IKK) complex. The phosphorylated NFKBIA is recognized by the E3 ligase complex leading to K48-linked ubiquitination, and targeted for ubiquitin-mediated proteasomal degradation, releasing the NF-kappa-B dimer p50/p65 (RelA:NFKB1) into the nucleus to turn on target genes (Karin M & Ben-Neriah Y 2000, Kanarek N & Ben-Neriah Y 2012; Hoffmann A et al. 2006). Crystal structures of NF-kappa-B inhibitors:NF-kappaB complexes revealed that an NF-kappa-B dimer binds to one IkB molecule (Jacobs MD & Harrison SC 1998; Ghosh G et 2012).
Literature References
PubMed ID
Title
Journal
Year
9865693
Structure of an IkappaBalpha/NF-kappaB complex
Jacobs, MD
,
Harrison, SC
Cell
1998
Participants
Input
NFkB inhibitor [cytosol]
(Homo sapiens)
NFKB1(1-433), NFKB2(1-454):RELA [cytosol]
(Homo sapiens)
Output
NFkB inhibitor:NFkB complex [cytosol]
(Homo sapiens)
Participates
as an event of
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
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NF-kappa-B inhibitor binds NF-kappa-B complex (Drosophila melanogaster)
NF-kappa-B inhibitor binds NF-kappa-B complex (Gallus gallus)
NF-kappa-B inhibitor binds NF-kappa-B complex (Mus musculus)
NF-kappa-B inhibitor binds NF-kappa-B complex (Rattus norvegicus)
NF-kappa-B inhibitor binds NF-kappa-B complex (Sus scrofa)
Authored
Shamovsky, V (2018-11-30)
Reviewed
de Martin, R (2022-05-04)
D'Eustachio, P (2018-12-04)
Created
Shamovsky, V (2018-12-04)
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