ArticleCell death and differentiation2015
NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- Lymphotoxin-driven cancer cell eradication by tumoricidal CD8bioRxiv : the preprint server for biology · 2025Article
- The path less traveled: the non-canonical NF-κB pathway in systemic lupus erythematosus.Frontiers in immunology · 2025Review
- Not just for lymphoid cells: the role of the noncanonical NF-κB signaling pathway in early and late myelopoiesis with a focus on hypereosinophilic disorders.Journal of leukocyte biology · 2024Review
- Different types of cell death and their shift in shaping disease.Cell death discovery · 2023Review
- Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases.Frontiers in immunology · 2023Review
- NF-κB Inducing Kinase Regulates Intestinal Immunity and Homeostasis.Frontiers in immunology · 2022Review
- An epithelialProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Targeting NF-κB-Inducing Kinase (NIK) in Immunity, Inflammation, and Cancer.International journal of molecular sciences · 2020Review
- TRAF3 Modulation: Novel Mechanism for the Anti-inflammatory Effects of the Vitamin D Receptor Agonist Paricalcitol in Renal Disease.Journal of the American Society of Nephrology : JASN · 2020Article
- Article
- Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation.Nature communications · 2019Article
- Adenovirus-mediated herpes simplex virus thymidine kinase gene therapy combined with ganciclovir induces hepatoma cell apoptosis.Experimental and therapeutic medicine · 2019Article
- The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications.Frontiers in oncology · 2019Review
- Preoperative short-term fasting protects liver injury in patients undergoing hepatectomy.Annals of translational medicine · 2018Article
- The non-canonical NF-κB pathway in immunity and inflammation.Nature reviews. Immunology · 2017Review
- Regulating the balance between necroptosis, apoptosis and inflammation by inhibitors of apoptosis proteins.Immunology and cell biology · 2017Review
- More to Life than NF-κB in TNFR1 Signaling.Trends in immunology · 2016Review
- Regulation of RIPK1's cell death function by phosphorylation.Cell cycle (Georgetown, Tex.) · 2016Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 5 countries.
Funding
Abstract
NF-κB-inducing kinase (NIK) is well-known for its role in promoting p100/NF-κB2 processing into p52, a process defined as the alternative, or non-canonical, NF-κB pathway. Here we reveal an unexpected new role of NIK in TNFR1-mediated RIP1-dependent apoptosis, a consequence of TNFR1 activation observed in c-IAP1/2-depleted conditions. We show that NIK stabilization, obtained by activation of the non-death TNFRs Fn14 or LTβR, is required for TNFα-mediated apoptosis. These apoptotic stimuli trigger the depletion of c-IAP1/2, the phosphorylation of RIP1 and the RIP1 kinase-dependent assembly of the RIP1/FADD/caspase-8 complex. In the absence of NIK, the phosphorylation of RIP1 and the formation of RIP1/FADD/caspase-8 complex are compromised while c-IAP1/2 depletion is unaffected. In vitro kinase assays revealed that recombinant RIP1 is a bona fide substrate of NIK. In vivo, we demonstrated the requirement of NIK pro-death function, but not the processing of its substrate p100 into p52, in a mouse model of TNFR1/LTβR-induced thymus involution. In addition, we also highlight a role for NIK in hepatocyte apoptosis in a mouse model of virus-induced TNFR1/RIP1-dependent liver damage. We conclude that NIK not only contributes to lymphoid organogenesis, inflammation and cell survival but also to TNFR1/RIP1-dependent cell death independently of the alternative NF-κB pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.