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Cell Res. 2011 Jan;21(1):71-85. doi: 10.1038/cr.2010.177. Epub 2010 Dec 21.

Non-canonical NF-κB signaling pathway.

Author information

1
Department of Immunology, The University of Texas MD Anderson Cancer Center, The University of Texas Graduate School of Biomedical Sciences at Houston, 7455 Fannin Street, Box 902, Houston, TX 77030, USA. ssun@mdanderson.org

Abstract

The non-canonical NF-κB pathway is an important arm of NF-κB signaling that predominantly targets activation of the p52/RelB NF-κB complex. This pathway depends on the inducible processing of p100, a molecule functioning as both the precursor of p52 and a RelB-specific inhibitor. A central signaling component of the non-canonical pathway is NF-κB-inducing kinase (NIK), which integrates signals from a subset of TNF receptor family members and activates a downstream kinase, IκB kinase-α (IKKα), for triggering p100 phosphorylation and processing. A unique mechanism of NIK regulation is through its fate control: the basal level of NIK is kept low by a TRAF-cIAP destruction complex and signal-induced non-canonical NF-κB signaling involves NIK stabilization. Tight control of the fate of NIK is important, since deregulated NIK accumulation is associated with lymphoid malignancies.

PMID:
21173796
PMCID:
PMC3193406
DOI:
10.1038/cr.2010.177
[Indexed for MEDLINE]
Free PMC Article

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