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NF-kappa-B complex is transported from cytosol to nucleus
Stable Identifier
R-HSA-168166
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
,
nucleoplasm
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 complex is transported from cytosol to nucleus (Homo sapiens)
Innate Immune System (Homo sapiens)
DDX58/IFIH1-mediated induction of interferon-alpha/beta (Homo sapiens)
TRAF6 mediated NF-kB activation (Homo sapiens)
NF-kappa-B complex is transported from cytosol to nucleus (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 complex is transported from cytosol to nucleus (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 complex is transported from cytosol to nucleus (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 complex is transported from cytosol to nucleus (Homo sapiens)
Toll Like Receptor 3 (TLR3) Cascade (Homo sapiens)
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
NF-kappa-B complex is transported from cytosol to nucleus (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 complex is transported from cytosol to nucleus (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 complex is transported from cytosol to nucleus (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 complex is transported from cytosol to nucleus (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 complex is transported from cytosol to nucleus (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 complex is transported from cytosol to nucleus (Homo sapiens)
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Though the signaling cascade is unclear, several pieces of experimental data suggest that activation of AGER leads to sustained activation and upregulation of NFkappaB, measured as NFkappaB translocation to the nucleus, and increased levels of de novo synthesized NFkappaB. NFkB is a family of transcription factors that play pivotal roles in immune, inflammatory, and antiapoptotic responses. There are five NF-kB/Rel family members, p65 (RelA), RelB, c-Rel, p50/p105 (NF-kappa-B1) and p52/p100 (NF-kappa-B2). All members of the NFkB family contain a highly conserved DNA-binding and dimerization domain called Rel-homology region (RHR). The RHR is responsible for homo- or heterodimerization. Therefore, NF-kappa-B exists in unstimulated cells as homo or heterodimers; the most common heterodimer is p65/p50. NF-kappa-B is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins called IkBs, which mask the nuclear localization signal of NF-kB and prevent its nuclear translocation. Various stimuli induce the activation of the IkB kinase (IKK) complex, which then phosphorylates IkBs. The phosphorylated IkBs are ubiquitinated and then degraded through the proteasome-mediated pathway. The degradation of IkBs releases NF-kappa-B and and it can be transported into nucleus where it induces the expression of target genes.
Literature References
PubMed ID
Title
Journal
Year
16056267
Ubiquitin signalling in the NF-kappaB pathway
Chen, ZJ
Nat Cell Biol
2005
15145317
The two NF-kappaB activation pathways and their role in innate and adaptive immunity
Karin, M
,
Bonizzi, G
Trends Immunol
2004
10723127
Activation of NF-kappa B by the dsRNA-dependent protein kinase, PKR involves the I kappa B kinase complex
Esteban, M
,
Alcami, J
,
Gil, J
Oncogene
2000
Participants
Input
NFKB1(1-433), NFKB2(1-454):RELA [cytosol]
(Homo sapiens)
Output
NFKB1(1-433), NFKB2(1-454):RELA [nucleoplasm]
(Homo sapiens)
Participates
as an event of
TAK1-dependent IKK and NF-kappa-B activation (Homo sapiens)
TRAF6 mediated NF-kB activation (Homo sapiens)
This event is regulated
Positively by
Regulator
AGER ligands:AGER [plasma membrane]
(Homo sapiens)
Orthologous Events
Released NFkB complex migrates to the nucleus and turns on transcription (Gallus gallus)
NF-kappa-B complex is transported from cytosol to nucleus (Bos taurus)
NF-kappa-B complex is transported from cytosol to nucleus (Canis familiaris)
NF-kappa-B complex is transported from cytosol to nucleus (Danio rerio)
NF-kappa-B complex is transported from cytosol to nucleus (Drosophila melanogaster)
NF-kappa-B complex is transported from cytosol to nucleus (Gallus gallus)
NF-kappa-B complex is transported from cytosol to nucleus (Mus musculus)
NF-kappa-B complex is transported from cytosol to nucleus (Rattus norvegicus)
NF-kappa-B complex is transported from cytosol to nucleus (Sus scrofa)
Authored
Shamovsky, V (2009-12-16)
Reviewed
de Martin, R (2022-05-04)
Wu, J (2013-05-22)
Jin, L (2013-05-22)
Mocarski, ES (2012-02-19)
Upton, JW (2012-02-19)
Fitzgerald, KA (2012-11-13)
D'Eustachio, P (2011-12-08)
Napetschnig, J (2012-11-16)
Created
Gillespie, ME (2005-11-10)
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