NFkB complex translocates from the cytosol to the nucleus

Stable Identifier
R-HSA-9604480
Type
Reaction [transition]
Species
Homo sapiens
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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 (NFkappa-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.

DExH/D-box helicase (DHX9)-mediated sensing of CpG-B trigger downstream signaling to NF-κappa B. Knockdown of DHX9 expression by RNA interference in the CpG-B-treated human plasmacytoid dendritic cell line Gen2.2 inhibited nuclear localization of p50 (NF-kappa-B1) subunit of NF-κappa B complex (Kim T et al. 2010).

DNA-dependent activator of IRFs/Z-DNA binding protein 1 (ZBP1 or DAI) recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB (Rebsamen M et al. 2009).

Literature References
PubMed ID Title Journal Year
19590578 DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB

Rebsamen, M, Heinz, LX, Meylan, E, Michallet, MC, Schroder, K, Hofmann, K, Vazquez, J, Benedict, CA, Tschopp, J

EMBO Rep 2009
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

Bonizzi, G, Karin, M

Trends Immunol 2004
20696886 Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells

Kim, T, Pazhoor, S, Bao, M, Zhang, Z, Hanabuchi, S, Facchinetti, V, Bover, L, Plumas, J, Chaperot, L, Qin, J, Liu, YJ

Proc. Natl. Acad. Sci. U.S.A. 2010
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