ArticleBMC biology2024
The protein phosphatase PP6 promotes RIPK1-dependent PANoptosis.
Article in BMC biology, 2024. 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.
- Article
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Review
- PANoptosis in life and death across cell types: From innate immunity to therapeutic implications.Cell chemical biology · 2026Review
- Pseudorabies virus infection induces IRF1-dependent PANoptosis to provoke the excessive release of HMGB1 and IL-1β.Communications biology · 2026Article
- Research progress on PANoptosis in diabetic cardiomyopathy.Journal of physiology and biochemistry · 2026Review
- Ripk1-dependent PANoptosis promotes EndMT and aggravates hypoglycemia-related cardiac fibrosis in diabetes.Journal of translational medicine · 2026Article
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Treatment of Inflammatory Bowel Disease with Drugs Targeting PANoptosis: A Comprehensive Review.Biomedicines · 2026Review
- Research progress in PANoptosis mechanisms and their interplay with tuberculosis.Frontiers in cellular and infection microbiology · 2026Review
- PANoptosis nexus in ischemia-reperfusion injury: from integrated cell death mechanisms to novel therapeutic opportunities.Frontiers in immunology · 2026Review
- PANoptosis: potential new targets and therapeutic prospects in digestive diseases.Apoptosis : an international journal on programmed cell death · 2025Review
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- Mitochondrial orchestration of PANoptosis: mechanisms, disease pathogenesis, and emerging therapeutic frontiers.Cell death discovery · 2025Review
- Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death.Cell death discovery · 2025Review
- PANoptosis: a potential target of atherosclerotic cardiovascular disease.Apoptosis : an international journal on programmed cell death · 2025Review
- Identification and Validation of Glycosylation‑Related Genes in Ischemic Stroke Based on Bioinformatics and Machine Learning.Journal of molecular neuroscience : MN · 2025Article
- Neuronal Injury after Ischemic Stroke: Mechanisms of Crosstalk Involving Necroptosis.Journal of molecular neuroscience : MN · 2025Review
- Targeting PSMB5-induced PANoptosis in bladder cancer: multi-omics insights and TCM candidate discovery.Frontiers in immunology · 2025Article
- Targeting PANoptosis in Bacterial-Induced Inflammatory Diseases: Mechanisms and Therapeutic Interventions.Journal of inflammation research · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
backgroundThe innate immune system serves as the first line of host defense. Transforming growth factor-β-activated kinase 1 (TAK1) is a key regulator of innate immunity, cell survival, and cellular homeostasis. Because of its importance in immunity, several pathogens have evolved to carry TAK1 inhibitors. In response, hosts have evolved to sense TAK1 inhibition and induce robust lytic cell death, PANoptosis, mediated by the RIPK1-PANoptosome. PANoptosis is a unique innate immune inflammatory lytic cell death pathway initiated by an innate immune sensor and driven by caspases and RIPKs. While PANoptosis can be beneficial to clear pathogens, excess activation is linked to pathology. Therefore, understanding the molecular mechanisms regulating TAK1 inhibitor (TAK1i)-induced PANoptosis is central to our understanding of RIPK1 in health and disease.
resultsIn this study, by analyzing results from a cell death-based CRISPR screen, we identified protein phosphatase 6 (PP6) holoenzyme components as regulators of TAK1i-induced PANoptosis. Loss of the PP6 enzymatic component, PPP6C, significantly reduced TAK1i-induced PANoptosis. Additionally, the PP6 regulatory subunits PPP6R1, PPP6R2, and PPP6R3 had redundant roles in regulating TAK1i-induced PANoptosis, and their combined depletion was required to block TAK1i-induced cell death. Mechanistically, PPP6C and its regulatory subunits promoted the pro-death S166 auto-phosphorylation of RIPK1 and led to a reduction in the pro-survival S321 phosphorylation.
conclusionsOverall, our findings demonstrate a key requirement for the phosphatase PP6 complex in the activation of TAK1i-induced, RIPK1-dependent PANoptosis, suggesting this complex could be therapeutically targeted in inflammatory conditions.
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