The Fas Signaling Pathway: More Than a Paradigm
Abstract
Apoptosis and related forms of cell death have central importance in development, homeostasis, tumor surveillance, and the function of the immune system. Apoptosis is initiated by two principal pathways. The intrinsic pathway emerges from mitochondria, whereas the extrinsic pathway is activated by the ligation of death receptors. This Viewpoint introduces the basic mechanisms of the extrinsic pathway, using the example of the prototypical death receptor Fas and its role in apoptosis, but it also points out the increasingly understood importance of this receptor as a non-apoptotic signal transducer.
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Death receptor activation depends on the binding of the cognate ligand(s).
“death receptors, whose activation depends on the binding of the cognate ligand(s)”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [270]
Extrinsic apoptosis is mostly driven by either death receptors or dependence receptors.
“Extrinsic apoptosis is mostly driven by either of two types of plasma membrane receptors: (1) death receptors, whose activation depends on the binding of the cognate ligand(s), and (2) dependence receptors, whose activation occurs when the levels of their specific ligand drop below a specific threshold [267 269–271].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [270]
Dependence receptor activation occurs when the levels of their specific ligand drop below a specific threshold.
“dependence receptors, whose activation occurs when the levels of their specific ligand drop below a specific threshold [267 269–271].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [270]
Death receptors include FAS, TNFRSF1A, TNFRSF10A, and TNFRSF10B.
“Death receptors include (but are not limited to): Fas cell surface death receptor (FAS; also known as CD95 or APO-1), and TNF receptor superfamily member 1A (TNFRSF1A; best known as TNFR1), 10a (TNFRSF10A; best known as TRAILR1 or DR4), and 10b (TNFRSF10B; best known as TRAILR2 or DR5) [269, 270, 272, 273].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [270]
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- Authors
- Wajant, H.
- Affiliations
- University of Stuttgart (DE)
- Corresponding author
- Wajant, Harald
- ORCID
- Wajant, Harald
- Venue
- Science
- Published
- 2002-05-31
- Volume
- 296
- Issue
- 5573
- Pages
- 1635-1636
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1988777405
- Cited by
- 957
- References
- 7
- Citations by year
- 2026: 13 · 2025: 27 · 2024: 31 · 2023: 37 · 2022: 36 · 2021: 39 · 2020: 44 · 2019: 42 · 2018: 43 · 2017: 41 · 2016: 53 · 2015: 48 · 2014: 54 · 2013: 51 · 2012: 52
- FWCI
- 15.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA81050, R01CA081050)
- National Institute of General Medical Sciences (F31GM065065, R01GM054508, GM54508)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK038761, DK 38761)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- Fas, Fas signaling pathway, apoptosis, extrinsic apoptotic pathway, death receptors, non-apoptotic signaling, signal transduction, cell death
- MeSH terms
- Animals, Carrier Proteins, Cell Division, Humans, Membrane Glycoproteins, Mitochondria, Models, Biological, Necrosis, Proteins, Signal Transduction, Apoptosis, fas Receptor, Caspases, Mitogen-Activated Protein Kinases, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, Fas-Associated Death Domain Protein, Fas Ligand Protein, Receptor-Interacting Protein Serine-Threonine Kinases, CASP8 and FADD-Like Apoptosis Regulating Protein
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