Non-canonical nuclear factor kappa B signaling pathway (Non-canonical NF-κB pathway)

The **non-canonical nuclear factor kappa B signaling pathway** is a distinct signaling route within the broader NF-κB family, primarily responsible for the activation of the p52/RelB transcription factor complex[1][3][4][6][7]. It is activated by specific members of the tumor necrosis factor receptor (TNFR) superfamily, such as BAFFR, CD40, lymphotoxin β-receptor, and RANK[2][3][6]. Central to this pathway is the NF-κB-inducing kinase (NIK, also known as MAP3K14), which upon activation leads to the phosphorylation and processing of the p100 protein into its active form, p52, via IKKα[1][4][6]. The resulting RelB:p52 heterodimer translocates to the nucleus, where it regulates genes involved in immune system development, lymphoid organogenesis, B-cell maturation, and osteoclast differentiation[3][5][7]. Unlike the canonical NF-κB pathway, this non-canonical route is slower, is less broadly responsive, and is tightly regulated through degradation of NIK by TRAF2/3 and cIAP1/2 complexes in the absence of activating signals[1][6]. Deregulation or chronic activation of the non-canonical pathway is implicated in autoimmune disease, chronic inflammation, and several B-cell lymphomas and other lymphoid malignancies[1][4][5]. **Notes for Structured Extraction:** - This is a **signaling pathway**, **not a druggable single protein target or receptor**, hence `is_target: false` and `is_incorrect: true`. - If the intended query was for a component protein (e.g., NIK/MAP3K14, IKKα, NF-κB2/p100/p52, or RelB), those should be addressed separately with entries specific to each molecule. - For curated database or structured purposes, the canonical form would point to the pathway or the core signaling protein NIK (MAP3K14) for drug targeting, not the pathway as a whole[1][4].

Other names

Non-canonical NF-κB signalingAlternative NF-κB pathwayNF-κB2 pathway