ArticleThe Journal of biological chemistry2016
γ-Secretase Activity Is Required for Regulated Intramembrane Proteolysis of Tumor Necrosis Factor (TNF) Receptor 1 and TNF-mediated Pro-apoptotic Signaling.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Use of an Intramolecular Quenched Fluorescence (IQF) Cleavage Assay for Assessing Enzyme Kinetics of Gamma-Secretase in Human Skin Fibroblasts and Keratinocytes.Methods in molecular biology (Clifton, N.J.) · 2027Article
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation.Cell communication and signaling : CCS · 2025Article
- Mutations in PSEN1 predispose inflammation in an astrocyte model of familial Alzheimer's disease through disrupted regulated intramembrane proteolysis.Molecular neurodegeneration · 2025Article
- Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model.Journal of Alzheimer's disease : JAD · 2025Article
- The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- A Non-Canonical p75HER2 Signaling Pathway Underlying Trastuzumab Action and Resistance in Breast Cancer.Cells · 2024Article
- Molecular signatures in prion disease: altered death receptor pathways in a mouse model.Journal of translational medicine · 2024Article
- Review
- γ-Secretase fanning the fire of innate immunity.Biochemical Society transactions · 2023Review
- Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation.FEBS letters · 2022Review
- Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis.The Journal of experimental medicine · 2022Article
- Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells.Cells · 2021Article
- Review
- Early-Onset Familial Alzheimer Disease Variant PSEN2 N141I Heterozygosity is Associated with Altered Microglia Phenotype.Journal of Alzheimer's disease : JAD · 2020Article
- Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 2019Article
- The Tumor Necrosis Factor Family: Family Conventions and Private Idiosyncrasies.Cold Spring Harbor perspectives in biology · 2018Review
- ST6Gal-I sialyltransferase promotes tumor necrosis factor (TNF)-mediated cancer cell survival via sialylation of the TNF receptor 1 (TNFR1) death receptor.The Journal of biological chemistry · 2018Article
- Protective role of cellular prion protein against TNFα-mediated inflammation through TACE α-secretase.Scientific reports · 2017Article
- Recent advances in understanding neurotrophin signaling.F1000Research · 2016Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The γ-secretase protease and associated regulated intramembrane proteolysis play an important role in controlling receptor-mediated intracellular signaling events, which have a central role in Alzheimer disease, cancer progression, and immune surveillance. An increasing number of γ-secretase substrates have a role in cytokine signaling, including the IL-6 receptor, IL-1 receptor type I, and IL-1 receptor type II. In this study, we show that following TNF-converting enzyme-mediated ectodomain shedding of TNF type I receptor (TNFR1), the membrane-bound TNFR1 C-terminal fragment is subsequently cleaved by γ-secretase to generate a cytosolic TNFR1 intracellular domain. We also show that clathrin-mediated internalization of TNFR1 C-terminal fragment is a prerequisite for efficient γ-secretase cleavage of TNFR1. Furthermore, using in vitro and in vivo model systems, we show that in the absence of presenilin expression and γ-secretase activity, TNF-mediated JNK activation was prevented, assembly of the TNFR1 pro-apoptotic complex II was reduced, and TNF-induced apoptosis was inhibited. These observations demonstrate that TNFR1 is a γ-secretase substrate and suggest that γ-secretase cleavage of TNFR1 represents a new layer of regulation that links the presenilins and the γ-secretase protease to pro-inflammatory cytokine signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.