NF-kappa-B complex is transported from cytosol to nucleus

Stable Identifier
Reaction [transition]
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
This event is regulated
Orthologous Events
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