The ‘complexities’ of life and death: Death receptor signalling platforms
Open accessAbstract
Cell death is critical to the normal functioning of multi-cellular organisms, playing a central role in development, immunity, inflammation, and cancer progression. Two cell death mechanisms, apoptosis and necroptosis, are dependent on the formation of distinct multi-protein complexes including the DISC, Apoptosome, Piddosome and Necrosome following the induction of cell death by specific stimuli. The role of several of these key multi-protein signalling platforms, namely the DISC, TNFR1 complex I/II, the Necrosome and Ripoptosome, in mediating these pathways will be discussed, as well as the open questions and potential therapeutic benefits of understanding their underlying mechanisms.
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Death receptor ligation generally allows assembly of a dynamic multiprotein complex at the intracellular tail (DISC, complex I, complex II) that regulates CASP8 (or CASP10) activation.
“As a general rule, death receptor ligation allows for the assembly of a dynamic multiprotein complex at the intracellular tail of the receptor, such as so-called “death-inducing signaling complex” (DISC), “complex I”, and “complex II”, which operate as molecular platforms to regulate the activation and functions of CASP8 (or CASP10, in a limited number of settings) [274–276].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [275]
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Self-citation
- Authors
- Dickens, L. S., Powley, I. R., Hughes, M. A., & MacFarlane, M.
- Affiliations
- University of Leicester (GB)
- Corresponding author
- MacFarlane, Marion
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 318
- Issue
- 11
- Pages
- 1269-1277
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2031456306
- Cited by
- 208
- References
- 73
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 11 · 2021: 16 · 2020: 17 · 2019: 14 · 2018: 13 · 2017: 22 · 2016: 22 · 2015: 17 · 2014: 22 · 2013: 16 · 2012: 7
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Experimental Cell Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- 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
- Social Sciences › Anthropology › Death, Funerary Practices, and Mourning
- Keywords
- cell death, death receptor signaling, apoptosis, necroptosis, death-inducing signalling complex, necrosome, ripoptosome, apoptosome, PIDDosome, cancer therapy
- MeSH terms
- Animals, Humans, Signal Transduction, Cell Death, Multiprotein Complexes, Receptors, Death Domain
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