TNF receptor subtype signalling: Differences and cellular consequences
Abstract
Tumour necrosis factor-alpha (TNF alpha) is a multifunctional cytokine belonging to a family of ligands with an associated family of receptor proteins. The pleiotropic actions of TNF range from proliferative responses such as cell growth and differentiation, to inflammatory effects and the mediation of immune responses, to destructive cellular outcomes such as apoptotic and necrotic cell death mechanisms. Activated TNF receptors mediate the association of distinct adaptor proteins that regulate a variety of signalling processes including kinase or phosphatase activation, lipase stimulation, and protease induction. Moreover, the cytokine regulates the activities of transcription factors, heterotrimeric or monomeric G-proteins and calcium ion homeostasis in order to orchestrate its cellular functions. This review addresses the structural basis of TNF signalling, the pathways employed with their cellular consequences, and focuses on the specific role played by each of the two TNF receptor isotypes, TNFR1 and TNFR2.
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TNF-α binds to TNFR1, leading to neuronal apoptosis.
“TNF-α has been reported to bind to tumor necrosis factor (TNFR1), leading to neuronal apoptosis [155,156].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [156]
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Exercise normalises overexpression of TNF-α in knockout mice
Keller, C., Keller, P., Giralt, M., Hidalgo, J., & Pedersen, B. K. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.06.129 · Cited by 110 · see citing works
Neuroinflammation microenvironment sharpens seizure circuit
Villasana‐Salazar, B., & Vezzani, A. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106027 · Cited by 106 · see citing works
- Authors
- MacEwan, D. J.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- MacEwan, David J.
- ORCID
- MacEwan, David J.
- Venue
- Cellular Signalling
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 14
- Issue
- 6
- Pages
- 477-492
- ISSN
- 0898-6568 (ISSN-L)
- OpenAlex
- W2069681479
- Cited by
- 610
- References
- 394
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 18 · 2021: 14 · 2020: 17 · 2019: 20 · 2018: 24 · 2017: 18 · 2016: 13 · 2015: 21 · 2014: 20 · 2013: 29 · 2012: 37
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Signalling (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- TNF-α, TNFR1, TNFR2, adaptor proteins, apoptosis, necrosis, transcription factors, G proteins, calcium homeostasis
- MeSH terms
- Animals, Models, Biological, Phospholipases, Phosphoprotein Phosphatases, Protein Kinases, Sphingomyelin Phosphodiesterase, Tumor Necrosis Factor-alpha, Signal Transduction, Antigens, CD, Receptors, Tumor Necrosis Factor, Caspases, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Mice
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