The noncanonical NF-?B pathway.

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The noncanonical NF-?B pathway.

Immunol Rev. 2012 Mar;246(1):125-40

Authors: Sun SC

Abstract
The noncanonical nuclear factor-?B (NF-?B) signaling pathway mediates activation of the p52/RelB NF-?B complex and, thereby, regulates specific immunological processes. This NF-?B pathway relies on the inducible processing of NF-?B2 precursor protein, p100, as opposed to the degradation of I?B? in the canonical NF-?B pathway. A central signaling component of the noncanonical NF-?B pathway is NF-?B-inducing kinase (NIK), which functions together with a downstream kinase, IKK? (inhibitor of NF-?B kinase ?), to induce phosphorylation-dependent ubiquitination and processing of p100. Under normal conditions, NIK is targeted for continuous degradation by a tumor necrosis factor (TNF) receptor-associated factor-3 (TRAF3)-dependent E3 ubiquitin ligase. In response to signals mediated by a subset of TNF receptor superfamily members, NIK becomes stabilized as a result of TRAF3 degradation, leading to the activation of noncanonical NF-?B. This review discusses both the historical perspectives and the recent progress in the regulation and biological function of the noncanonical NF-?B pathway.

PMID: 22435551 [PubMed - indexed for MEDLINE]

NF-kB pathway NF-kB signaling NF-kappaB signaling pathway