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PMID: 22435551 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

The noncanonical NF-κB pathway.

Immunological reviews ·Vol. 246 ·No. 1 ·2012-03-00 ·Pages 125-40

Sun SC

Abstract

The noncanonical nuclear factor-κB (NF-κB) signaling pathway mediates activation of the p52/RelB NF-κB complex and, thereby, regulates specific immunological processes. This NF-κB pathway relies on the inducible processing of NF-κB2 precursor protein, p100, as opposed to the degradation of IκBα in the canonical NF-κB pathway. A central signaling component of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which functions together with a downstream kinase, IKKα (inhibitor of NF-κB kinase α), 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-κB. This review discusses both the historical perspectives and the recent progress in the regulation and biological function of the noncanonical NF-κB pathway.

MeSH Terms
Animals Humans NF-kappa B/metabolism NF-kappa B p52 Subunit/metabolism Protein Serine-Threonine Kinases/metabolism Signal Transduction
Chemicals
NF-kappa B NF-kappa B p52 Subunit Protein Serine-Threonine Kinases NF-kappa B kinase
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Sun Shao-Cong
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ssun@mdanderson.org
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Article Info
Journal
Immunological reviews
Abbr.
Immunol Rev
ISSN
1600-065X
DOI
10.1111/j.1600-065X.2011.01088.x
Email
ssun@mdanderson.org
Published
2012-03-00
Pages
125-40
Language
English
Region
England
NLM ID
7702118
PMCID
PMC3313452
Subset
IM
Grants
NIAID NIH HHS · R01 AI064639 · United States
NIAID NIH HHS · AI064639 · United States
NIAID NIH HHS · R01 AI057555 · United States
NIAID NIH HHS · R37 AI064639 · United States
NIAID NIH HHS · R01 AI064639-07 · United States
NIGMS NIH HHS · GM84459-S1 · United States
NIAID NIH HHS · AI057555 · United States
NIGMS NIH HHS · R01 GM084459 · United States
NIGMS NIH HHS · GM84459 · United States
NIAID NIH HHS · R01 AI057555-10 · United States
NIGMS NIH HHS · R01 GM084459-08S1 · United States
NIGMS NIH HHS · R01 GM084459-10 · United States
External Links
PubMed source DOI: 10.1111/j.1600-065X.2011.01088.x PMC Full Text View journal details
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