The Role of the Kinases RIP1 and RIP3 in TNF-Induced Necrosis
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Programmed necrosis in response to TNF requires the activity of two serine-threonine kinases.
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Upon necroptosis initiation by TNFR1, RIPK3 is activated by RIPK1 (provided CASP8 is inactive) through mechanism involving physical interaction between their RHIM domains and RIPK1 catalytic activity.
“Upon necroptosis initiation by TNFR1, RIPK3 is activated by RIPK1 (provided that CASP8 is inactive, see below) through a mechanism involving the physical interaction between their respective RIP homotypic interaction motif (RHIM) domains and RIPK1 catalytic activity [436–438].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [436]
Activation of RIPK3 downstream of TNFR1 ligation relies on formation of RIPK1-containing and RIPK3-containing amyloid-like signaling complex known as necrosome, wherein first RIPK1 and then RIPK3 undergo trans-phosphorylation or auto-phosphorylation events required for MLKL recruitment and necroptosis activation.
“In particular, the activation of RIPK3 downstream of TNFR1 ligation relies on the formation of a RIPK1-containing and RIPK3-containing amyloid-like signaling complex commonly known as necrosome [436, 470], wherein first RIPK1 and then RIPK3 undergo a series of trans-phosphorylation or auto-phosphorylation events that are required for MLKL recruitment and necroptosis activation [437, 438, 442, 471]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [436]
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- Authors
- Vandenabeele, P., Declercq, W., Van Herreweghe, F., & Vanden Berghe, T.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, 9052 Zwijnaarde, Belgium.
- Corresponding author
- Vandenabeele, Peter
- Venue
- Science Signaling
- Published
- 2010-03-30
- Volume
- 3
- Issue
- 115
- Pages
- re4-re4
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- OpenAlex
- W2160651627
- Cited by
- 482
- References
- 6
- Citations by year
- 2026: 6 · 2025: 25 · 2024: 18 · 2023: 25 · 2022: 20 · 2021: 30 · 2020: 19 · 2019: 27 · 2018: 34 · 2017: 29 · 2016: 45 · 2015: 30 · 2014: 44 · 2013: 39 · 2012: 48
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- other-oa
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- RIPK1, RIPK3, necrosome, TNF receptor signaling, caspase regulation, ubiquitination, reactive oxygen species, mitochondrial complex I, NADPH oxidase, calcium mobilization, phospholipase A2, lipoxygenase, acid sphingomyelinase, lysosomal destabilization, glutaminolysis, glycolytic flux, immunogenic cell death, neurodegeneration
- MeSH terms
- Animals, Humans, Mitochondria, Necrosis, Neoplasms, Tumor Necrosis Factor-alpha, Signal Transduction, Reperfusion Injury, RNA-Binding Proteins, Apoptosis, Reactive Oxygen Species, Caspases, Ubiquitin, Nuclear Pore Complex Proteins, Mice, Receptor-Interacting Protein Serine-Threonine Kinases
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