ArticleNature communications2025
RIOK2 kinase regulates the translocation of the FADD-RIPK1-Caspase-8 complex to the ER and the cleavage of Gasdermin D to drive pyroptosis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Endoplasmic Reticulum-Targeting NIR Cyanine ER800 Nanoparticles Promote Pyroptosis in Triple-Negative Breast Cancer.ACS applied materials & interfaces · 2026Article
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Necroptosis in asthma: a critical driver of immune dysregulation and airway remodeling.Frontiers in immunology · 2026Review
- Decoding the molecular mechanisms of pyroptosis and its therapeutic development prospects.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophage infection by the pathogenic bacteria Yersinia or mimic stimulation of lipopolysaccharide (LPS) and transforming growth factor-β-activated kinase 1 (TAK1) inhibitor or tumor necrosis factor (TNF) and TAK1 inhibitor induces caspase-8-mediated gasdermin D (GSDMD) cleavage and pyroptosis. However, the upstream regulator of caspase-8-dependent cleavage of GSDMD remains elusive. Here we show that Serine/threonine-protein kinase RIO2 (RIOK2) interacts with the Fas-associated protein with death domain (FADD) and is essential for caspase-8-driven GSDMD cleavage. RIOK2's kinase activity drives the transport of lysosome to ER through activating myosin II and thereby translocate FADD-RIPK1-caspase-8 complex from lysosome to ER. Importantly, RIOK2's ATPase activity enhances its binding to this complex and directly triggers caspase-8 and gasdermin D cleavage both at ER and in vitro. Furthermore, RIOK2-mediated pyroptosis enhances host defense against Yersinia infection. Thus, our findings define an upstream regulator of caspase-8-dependent pyroptosis, implying a role of organelle crosstalk in spatial cleavage of gasdermins.
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