ArticleCell death & disease2016
TAK1 regulates caspase 8 activation and necroptotic signaling via multiple cell death checkpoints.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- Reduced endothelial TAK1 impairs vascular integrity in cerebral small vessel diseaseStroke and vascular neurology · 2026Article
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Molybdenum and cadmium co-induced apoptosis and necroptosis via activating endoplasmic reticulum stress and upregulating Caspase-8 expression in duck hepatocytes.Poultry science · 2026Article
- Cardiomyocyte programmed cell death in dilated cardiomyopathy: molecular crosstalk and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Beyond apoptosis: Exploring necroptosis, ferroptosis, and pyroptosis in sevoflurane- and isoflurane-associated PNDs.IBRO neuroscience reports · 2025Review
- Targeting tumor intrinsic TAK1 engages TNF-α-driven cell death through distinct mechanisms and enhances cancer immunotherapy.Cell death & disease · 2025Article
- Transforming Growth Factor-β-Activated Protein 1 (TAK1) Regulates Necroptosis in Age-Related Hearing Loss.Aging cell · 2025Article
- Understanding TAK1 deficiency in microglia: Dual mechanisms for photoreceptor protection in a mouse model of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Neuronal Injury after Ischemic Stroke: Mechanisms of Crosstalk Involving Necroptosis.Journal of molecular neuroscience : MN · 2025Review
- RIPK1 in necroptosis and recent progress in related pharmaceutics.Frontiers in immunology · 2025Review
- METTL3 restricts RIPK1-dependent cell death via the ATF3-cFLIP axis in the intestinal epithelium.Cell regeneration (London, England) · 2024Article
- Influenza virus infection activates TAK1 to suppress RIPK3-independent apoptosis and RIPK1-dependent necroptosis.Cell communication and signaling : CCS · 2024Article
- Thrombospondin-1 Regulates Trophoblast Necroptosis via NEDD4-Mediated Ubiquitination of TAK1 in Preeclampsia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- TAK1 Reduces Surgery-induced Overactivation of RIPK1 to Relieve Neuroinflammation and Cognitive Dysfunction in Aged Rats.Neurochemical research · 2023Article
- Ferroptosis contributes to catecholamine-induced cardiotoxicity and pathological remodeling.Free radical biology & medicine · 2023Article
- TAK1 Improves Cognitive Function via Suppressing RIPK1-Driven Neuronal Apoptosis and Necroptosis in Rats with Chronic Hypertension.Aging and disease · 2023Article
- Oxidative stress induces mitochondrial iron overload and ferroptotic cell death.Scientific reports · 2023Article
- Establishment of a novel signature to predict prognosis and immune characteristics of pancreatic cancer based on necroptosis-related long non-coding RNA.Molecular biology reports · 2023Article
- Notoginsenoside R1 protects against myocardial ischemia/reperfusion injury in mice via suppressing TAK1-JNK/p38 signaling.Acta pharmacologica Sinica · 2023Article
- Necroptosis in heart disease: Molecular mechanisms and therapeutic implications.Journal of molecular and cellular cardiology · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFβ-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, although the underlying molecular regulatory mechanisms are not well defined. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8-mediated apoptotic signaling through both NFκB-dependent and -independent mechanisms. Inhibition of TAK1 promoted TNFα-induced cell death through the induction of RIP1 phosphorylation/activation and necrosome formation. Further, inhibition of TAK1 triggered two caspase 8 activation pathways through the induction of RIP1-FADD-caspase 8 complex as well as FLIP cleavage/degradation. Mechanistically, our data uncovered an essential role for the adaptor protein TNF receptor-associated protein with death domain (TRADD) in caspase 8 activation and necrosome formation triggered by TAK1 inhibition. Moreover, ablation of the deubiqutinase CYLD prevented both apoptotic and necroptotic signaling induced by TAK1 inhibition. Finally, blocking the ubiquitin-proteasome pathway prevented the degradation of key pro-survival signaling proteins and necrosome formation. Thus, we identified new regulatory mechanisms underlying the critical role of TAK1 in cell survival through regulation of multiple cell death checkpoints. Targeting key components of the necroptotic pathway (e.g., TRADD and CYLD) and the ubiquitin-proteasome pathway may represent novel therapeutic strategies for pathological conditions driven by necroptosis.
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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.