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Cited by 355Cell death mechanisms and regulationinterferon and immune responsesNF-κB Signaling Pathways

Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases

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Thapa, Roshan J., Nogusa, Shoko, Chen, Peirong, Maki, Jenny L., Lerro, Anthony, Andrake, Mark, Rall, Glenn F., Degterev, Alexei +1 more·2013·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1301218110PMC PMC3746924
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Abstract

Significance: The interferons are small secreted proteins with powerful antiviral and cytotoxic properties. Here, we outline a signaling pathway activated by interferons that results in the precipitous necrotic death of susceptible cells. Interferon-induced necrosis proceeds via a novel, progressive mechanism that requires RNA transcription, as well as the sequential activity of three serine-threonine kinases: PKR, RIP1, and RIP3. This pronecrotic kinase cascade is normally held in check by FADD and caspases. As FADD can be disabled by phosphorylation during mitosis, our findings suggest the existence of a putative cell cycle-dependent checkpoint that licenses interferon-induced necrosis.

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Research works printed but not linked: 28

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Cited by

Sorted by citations

Authors
Thapa, R. J., Nogusa, S., Chen, P., Maki, J. L., Lerro, A., Andrake, M., Rall, G. F., Degterev, A., & Balachandran, S.
Affiliations
  • Fox Chase Cancer Center (US)
  • Tufts University (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2013-07-29
Volume
110
Issue
33
Pages
E3109-18
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1301218110
PMC
PMC3746924
OpenAlex
W1989739325
Cited by
355
References
6
Citations by year
2026: 17 · 2025: 22 · 2024: 26 · 2023: 27 · 2022: 22 · 2021: 40 · 2020: 16 · 2019: 20 · 2018: 35 · 2017: 23 · 2016: 34 · 2015: 27 · 2014: 43 · 2013: 3
FWCI
15.96
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (T32CA009035, 5T32 CA9035-37)
  • National Institute of General Medical Sciences (R01GM084205, GM084205)
  • National Institute of Allergy and Infectious Diseases (R21AI104212)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
necrosome, FADD, caspase-8, PKR, type I interferon, interferon-gamma, JAK1/STAT1 signaling, embryonic lethality
MeSH terms
Animals, Cells, Cultured, Electrophoresis, Polyacrylamide Gel, Interferon-gamma, Models, Molecular, Necrosis, Phosphorylation, Signal Transduction, Mice, Knockout, eIF-2 Kinase, GTPase-Activating Proteins, RNA Interference, Immunoprecipitation, STAT1 Transcription Factor, Mice, Fas-Associated Death Domain Protein, Receptor-Interacting Protein Serine-Threonine Kinases, Cell Cycle Checkpoints

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