The Death Domain Kinase RIP Mediates the TNF-Induced NF-κB Signal
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The death domain serine/threonine kinase RIP interacts with the death receptors Fas and tumor necrosis receptor 1 (TNFR1). In vitro, RIP stimulates apoptosis, SAPK/JNK, and NF-kappaB activation. To define the physiologic role(s) that RIP plays in regulating apoptosis in vivo, we introduced a rip null mutation in mice through homologous recombination. RIP-deficient mice appear normal at birth but fail to thrive, displaying extensive apoptosis in both the lymphoid and adipose tissue and dying at 1-3 days of age. In contrast to a normal thymic anti-Fas response, rip-/- cells are highly sensitive to TNFalpha-induced cell death. Sensitivity to TNFalpha-mediated cell death in rip-/- cells is accompanied by a failure to activate the transcription factor NF-kappaB.
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At least in some settings, this reflects major role of RIPK1 in NF-κB activation.
“At least in some settings, this reflects the major role of RIPK1 in NF-κB activation [505–507].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [507]
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Kutscher, L. M., & Shaham, S. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.20 · Cited by 67 · see citing works
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- Authors
- Kelliher, M. A., Grimm, S., Ishida, Y., Kuo, F., Stanger, B. Z., & Leder, P.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Leder, Philip
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 1998-03
- Volume
- 8
- Issue
- 3
- Pages
- 297-303
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2124202816
- Cited by
- 1,102
- References
- 43
- Citations by year
- 2026: 13 · 2025: 26 · 2024: 30 · 2023: 19 · 2022: 25 · 2021: 28 · 2020: 31 · 2019: 43 · 2018: 39 · 2017: 38 · 2016: 47 · 2015: 30 · 2014: 61 · 2013: 36 · 2012: 28
- FWCI
- 25.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- RIP kinases, TNF-induced apoptosis, NF-κB activation, TNF receptor 1, Fas, SAPK/JNK, death receptor signaling
- MeSH terms
- Adipose Tissue, Animals, Failure to Thrive, Genes, Lethal, Lymphoid Tissue, Mice, Mutant Strains, Proteins, Tumor Necrosis Factor-alpha, Cytokines, NF-kappa B, Apoptosis, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, fas Receptor, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Mice, Receptor-Interacting Protein Serine-Threonine Kinases
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