Reactome | NFkB complex translocates from the cytosol to the nucleus

NFkB complex translocates from the cytosol to the nucleus

Stable Identifier

R-HSA-9604480

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

ReviewStatus

5/5

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NFkB complex translocates from the cytosol to the nucleus

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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
16056267	Ubiquitin signalling in the NF-kappaB pathway Chen, ZJ	Nat Cell Biol	2005
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
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