Regulation of NF-kappa B signaling

Stable Identifier
R-HSA-9758274
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Pathway
Species
Homo sapiens
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Nuclear factor kappa B (NF-kappa-B, NF-κB) is activated by a diverse range of stimuli including cytokines, ligands of pattern-recognition receptors (PRRs) such as Toll-like receptors (TLRs) in myeloid cells, antigen-activated TCR in T-cells and by DNA damage (reviewed in Yu H et al. 2020; Zhang T et al. 2021). NF-kappa-B regulates the transcription of genes that are involved in immune and inflammatory responses, cell cycle, cell proliferation and apoptosis (Bhatt D & Ghosh S 2014; Liu T et al. 2017; Yu H et al. 2020). In unstimulated cells, NF-κB is sequestered in the cytosol through interactions with a class of inhibitor proteins, called NF-κB inhibitors (IkBs, such as NFKBIA or NFKBIB) (Jacobs MD & Harrison SC 1998). IkBs mask the nuclear localization signal (NLS) of NF-κB preventing its nuclear translocation (Cervantes CF et al. 2011). A key event in NF-κB activation involves phosphorylation of IkBs by the IκB kinase (IKK) complex which consists of CHUK, IKBKB and IKBKG subunits (Israël A 2010). The activated NF-κB signaling is tightly controlled at multiple levels (Dorrington MG & Fraser IDC 2019; Prescott JA et al. 2021). Dysregulated NF-κB activity can cause tissue damage associated with inflammatory diseases and is also linked to tumorigenesis (Aggarwal BB & Sung B 2011; Liu T et al.2017; Barnabei L et al. 2021). The regulation of NF-κB is cell-type-, context- , and stimulus-dependent and is crucial for orchestrating specific cellular responses (Mussbacher M et al. 2019).

This Reactome module describes several molecular mechanisms that regulate TLR-mediated NF-κB signaling at the level of the IKK signaling complex.

Literature References
PubMed ID Title Journal Year
34269817 Inhibitory feedback control of NF-κB signalling in health and disease

Cook, SJ, Prescott, JA, Mitchell, JP

Biochem J 2021
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