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IKBIP binds IKBKB and CHUK
Stable Identifier
R-HSA-9749494
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
,
endoplasmic reticulum membrane
Synonyms
IKBIP binds IKBKB and IKBKA
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)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (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)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (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)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (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)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (Homo sapiens)
Toll Like Receptor 3 (TLR3) Cascade (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (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)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (Homo sapiens)
MyD88:MAL(TIRAP) cascade initiated on plasma membrane (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (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)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (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)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (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)
Regulation of NF-kappa B signaling (Homo sapiens)
IKBIP binds IKBKB and CHUK (Homo sapiens)
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The I-kappa-B-kinase (IKK) complex consists of two catalytic subunits, IKBKA (KKα or CHUK) and IKBKB (IKKβ), associated with a regulatory subunit IKBKG (NEMO). Yeast two-hybrid screening identified inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP or IKIP) as an IKBKB-binding protein (Hofer-Warbinek R et al. 2004). IKBIP was found to downregulate NF-kappa-B activation and induction of proinflammatory cytokines in human and mouse myeloid cells in response to Toll-like receptor (TLR) ligands (Wu H et al. 2020). In addition, IKBIP deficiency resulted in prolonged phosphorylation of IKBKB, CHUK and p65, and increased expression of NF-kappaB-responsive genes in myeloid cells after stimulation with LPS, TNF-α, and IL-1β. Moreover, IKBIP co-immunoprecipitated with IKBKA (CHUK) and IKBKB subunits, but not with IKBKG, upon co-expression of tagged proteins in human embryonic kidney HEK293T cells (Wu H et al. 2020). Mutagenesis analysis revealed that the N-terminal region of IKBIP interacts with leucine zipper (LZ) and helix-loop-helix (HLH) domains of IKBKB. Confocal microscopy showed that IKBKB colocalizes with IKBIP in the endoplasmic reticulum (ER) upon co-expression of tagged proteins in Hela cells (Wu H et al. 2020). These data suggest that IKBIP negatively regulates NF-kappa-B activation via targeting IKBKB and CHUK and inhibiting their phosphorylation (Wu H et al. 2020).
Literature References
PubMed ID
Title
Journal
Year
31826938
IKIP Negatively Regulates NF-κB Activation and Inflammation through Inhibition of IKKα/β Phosphorylation
Zhao, X
,
Liu, H
,
Wu, H
,
Zhang, L
,
Zheng, Y
,
Liu, B
,
Gao, C
J Immunol
2020
Participants
Input
CHUK [cytosol]
(Homo sapiens)
IKBIP [endoplasmic reticulum membrane]
(Homo sapiens)
IKBKB [cytosol]
(Homo sapiens)
Output
CHUK:IKBKB:IKBIP [endoplasmic reticulum membrane]
(Homo sapiens)
Participates
as an event of
Regulation of NF-kappa B signaling (Homo sapiens)
Event Information
Go Biological Process
negative regulation of I-kappaB kinase/NF-kappaB signaling (0043124)
Orthologous Events
IKBIP binds IKBKB and CHUK (Bos taurus)
Authored
Shamovsky, V (2021-11-12)
Reviewed
de Martin, R (2022-05-04)
D'Eustachio, P (2022-01-05)
Created
Shamovsky, V (2021-08-04)
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