non-canonical NF-kappaB signal transduction

Definition

Target type: biologicalprocess

An intracellular signaling cassette characterized by the NIK-dependent processing and activation of NF-kappaB. Begins with activation of the NF-kappaB-inducing kinase (NIK), which in turn phosphorylates and activates IkappaB kinase alpha (IKKalpha). IKKalpha phosphorylates the NF-kappa B2 protein (p100) leading to p100 processing and release of an active NF-kappaB (p52). The non-canonical NF-kappaB signaling pathway is generally activated by ligands of the TNF receptor superfamily, including lymphotoxin beta (LTB), CD40, OX40, RANK, TWEAK and B cell-activating factor (BAFF). [GOC:bf, GOC:mg2, GOC:signaling, GOC:vs, PMID:11239468, PMID:15140882, PMID:34659217]

Non-canonical NF-κB signaling is a distinct pathway from the canonical pathway, which is triggered by TNFα, IL-1β, and other pro-inflammatory stimuli. It is initiated by a family of transmembrane receptors, including members of the tumor necrosis factor receptor (TNFR) superfamily, such as CD40, lymphotoxin β receptor (LTβR), and BAFF receptor. Upon receptor activation, the intracellular domain of these receptors interacts with the adaptor molecule TRAF3, which recruits the kinase NIK (NF-κB-inducing kinase). NIK then phosphorylates and activates IKKα, a member of the IκB kinase family. Activated IKKα phosphorylates the NF-κB precursor protein p100, which is a subunit of the NF-κB complex. Phosphorylation of p100 triggers its ubiquitination and subsequent processing by the proteasome, leading to the generation of the active NF-κB subunit p52. p52 then forms a dimer with the RelB subunit, which translocates to the nucleus and activates target genes. Non-canonical NF-κB signaling is essential for various biological processes, including lymphoid organogenesis, B cell development, and immune responses. It plays a role in the regulation of the expression of genes involved in inflammation, cell survival, and immune cell differentiation. For instance, it controls the expression of lymphotoxin α (LTα), a key cytokine required for the formation of secondary lymphoid organs, such as lymph nodes and Peyer's patches. Moreover, it influences the production of chemokines and adhesion molecules, which are involved in the recruitment and activation of immune cells to sites of inflammation. Aberrant activation of non-canonical NF-κB signaling has been implicated in the pathogenesis of various diseases, including autoimmune disorders, cancer, and inflammatory bowel disease. The complex interplay between the canonical and non-canonical NF-κB signaling pathways underscores the critical role of this signaling network in maintaining cellular homeostasis and regulating immune responses.'
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Proteins (12)

Compounds (392)