Cited by 1,102NF-κB Signaling PathwaysCell death mechanisms and regulationImmune Response and Inflammation

The Death Domain Kinase RIP Mediates the TNF-Induced NF-κB Signal

Open access
Kelliher, Michelle A, Grimm, Stefan, Ishida, Yasumasa, Kuo, Frank, Stanger, Ben Z, Leder, Philip·1998·Immunity

Abstract

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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Crossref · 10.1016/s1074-7613(00)80535-x

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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
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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