ArticleThe Journal of cell biology2008
TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha.
Article in The Journal of cell biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
143 citing papers in PubMed, 236 citations in OpenAlex.
- Necroptosis in both tumour and stromal compartments determines responsiveness to immunogenic cell death-based immunotherapy.Nature communications · 2026Article
- CagA-dependent expression of anti-inflammatory cytokine IL-13 and TNFRSF member Fn14 inFrontiers in microbiology · 2026Article
- Deubiquitinase-dependent transcriptional silencing controls inflammation.Cell research · 2025Article
- Single-cell analyses unravel ecosystem dynamics and intercellular crosstalk during gallbladder cancer malignant transformation.Hepatology communications · 2025Article
- Inflammation and cancer cell survival: TRAF2 as a key player.Cell death & disease · 2025Review
- 1'-Acetoxychavicol Acetate Selectively Downregulates Tumor Necrosis Factor Receptor-Associated Factor 2 (TRAF2) Expression.Molecules (Basel, Switzerland) · 2025Article
- Targeting Fn14 as a therapeutic target for cachexia reprograms the glycolytic pathway in tumour and brain in mice.European journal of nuclear medicine and molecular imaging · 2024Article
- TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer.Nature communications · 2024Article
- TWEAK promotes inflammatory response in liver fibrosis.Journal of biochemical and molecular toxicology · 2023Article
- Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance.The EMBO journal · 2023Article
- Death by TNF: a road to inflammation.Nature reviews. Immunology · 2023Review
- Mechanism of skeletal muscle atrophy after spinal cord injury: A narrative review.Frontiers in nutrition · 2023Review
- Proteolytically generated soluble Tweak Receptor Fn14 is a blood biomarker for γ-secretase activity.EMBO molecular medicine · 2022Article
- Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-κB signaling.Disease models & mechanisms · 2022Article
- Review
- Inhibition of TWEAK/Tnfrsf12a axis protects against acute liver failure by suppressing RIPK1-dependent apoptosis.Cell death discovery · 2022Article
- Deubiquitinases in cell death and inflammation.The Biochemical journal · 2022Review
- Review
- Cytoplasmic and Nuclear Functions of cIAP1.Biomolecules · 2022Review
- Targeting fibroblast growth factor (FGF)-inducible 14 (Fn14) for tumor therapy.Frontiers in pharmacology · 2022Review
83 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byTWEAKing death.2008
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic inhibitor of apoptosis (IAP) antagonists induce degradation of IAP proteins such as cellular IAP1 (cIAP1), activate nuclear factor kappaB (NF-kappaB) signaling, and sensitize cells to tumor necrosis factor alpha (TNFalpha). The physiological relevance of these discoveries to cIAP1 function remains undetermined. We show that upon ligand binding, the TNF superfamily receptor FN14 recruits a cIAP1-Tnf receptor-associated factor 2 (TRAF2) complex. Unlike IAP antagonists that cause rapid proteasomal degradation of cIAP1, signaling by FN14 promotes the lysosomal degradation of cIAP1-TRAF2 in a cIAP1-dependent manner. TNF-like weak inducer of apoptosis (TWEAK)/FN14 signaling nevertheless promotes the same noncanonical NF-kappaB signaling elicited by IAP antagonists and, in sensitive cells, the same autocrine TNFalpha-induced death occurs. TWEAK-induced loss of the cIAP1-TRAF2 complex sensitizes immortalized and minimally passaged tumor cells to TNFalpha-induced death, whereas primary cells remain resistant. Conversely, cIAP1-TRAF2 complex overexpression limits FN14 signaling and protects tumor cells from TWEAK-induced TNFalpha sensitization. Lysosomal degradation of cIAP1-TRAF2 by TWEAK/FN14 therefore critically alters the balance of life/death signals emanating from TNF-R1 in immortalized cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.