The noncanonical NF-κB pathway
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 t...
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| Published in | Immunological reviews Vol. 246; no. 1; pp. 125 - 140 |
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| Main Author | |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.03.2012
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| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | The noncanonical nuclear factor- Kappa B (NF- Kappa B) signaling pathway mediates activation of the p52/RelB NF- Kappa B complex and, thereby, regulates specific immunological processes. This NF- Kappa B pathway relies on the inducible processing of NF- Kappa B2 precursor protein, p100, as opposed to the degradation of I Kappa B alpha in the canonical NF- Kappa B pathway. A central signaling component of the noncanonical NF- Kappa B pathway is NF- Kappa B-inducing kinase (NIK), which functions together with a downstream kinase, IKK alpha (inhibitor of NF- Kappa B kinase alpha ), 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- Kappa B. This review discusses both the historical perspectives and the recent progress in the regulation and biological function of the noncanonical NF- Kappa B pathway. 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. 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, inhibitor of NF-κB kinase α (IKKα), 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. 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.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. |
| Author | Sun, Shao-Cong |
| Author_xml | – sequence: 1 givenname: Shao-Cong surname: Sun fullname: Sun, Shao-Cong organization: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22435551$$D View this record in MEDLINE/PubMed |
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| Snippet | The noncanonical nuclear factor‐κB (NF‐κB) signaling pathway mediates activation of the p52/RelB NF‐κB complex and, thereby, regulates specific immunological... The noncanonical nuclear factor-κB (NF-κB) signaling pathway mediates activation of the p52/RelB NF-κB complex and, thereby, regulates specific immunological... The noncanonical nuclear factor- Kappa B (NF- Kappa B) signaling pathway mediates activation of the p52/RelB NF- Kappa B complex and, thereby, regulates... |
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| SubjectTerms | Animals cIAP Humans NF- Kappa B protein NF- Kappa B-inducing kinase NF-kappa B - metabolism NF-kappa B p52 Subunit - metabolism NF-kappaB-Inducing Kinase NIK noncanonical NF-κB p100 processing Protein Serine-Threonine Kinases - metabolism RelB protein Signal Transduction TRAF2 TRAF3 Tumor necrosis factor Tumor necrosis factor receptors Ubiquitin-protein ligase ubiquitination |
| Title | The noncanonical NF-κB pathway |
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