ArticleProceedings of the National Academy of Sciences of the United States of America2021
Necroptosis activates UPR sensors without disrupting their binding with GRP78.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Necroptosis-related diseases are regulated by the unfolded protein response during endoplasmic reticulum stress.Genes & diseases · 2027Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Evolution and Functional Implications of Codon Usage Bias in Eukaryotes.Journal of molecular evolution · 2026Review
- RIP3 and MLKL regulate ER stress in alcohol-associated liver disease and pharmacological ER stress models: Insights beyond necroptosis.JHEP reports : innovation in hepatology · 2026Article
- Ferroptosis, pyroptosis, and necroptosis in melanoma: regulatory cell death pathways and their implications for immunotherapy.Frontiers in oncology · 2026Review
- RIP3 and MLKL regulate Hepatic ER stress in alcohol-associated liver disease and pharmacological ER stress models: insights beyond necroptosis.bioRxiv : the preprint server for biology · 2025Article
- Cell death signaling in human erythron: erythrocytes lose the complexity of cell death machinery upon maturation.Apoptosis : an international journal on programmed cell death · 2025Review
- Organellophagy regulates cell death:A potential therapeutic target for inflammatory diseases.Journal of advanced research · 2025Review
- The Effects of Circadian Rhythm on Lead-Induced Toxicity in the DBC1.2 Olfactory Dark Basal Cell Line.Cells · 2025Article
- MLKL as an emerging machinery for modulating organelle dynamics: regulatory mechanisms, pathophysiological significance, and targeted therapeutics.Frontiers in pharmacology · 2025Review
- Glucose-Regulated Protein 78, via Releasing β-Catenin from Adherens Junctions, Facilitates Its Interaction with STAT3 in Mediating Retinal Neovascularization.The American journal of pathology · 2024Article
- The relationship between endoplasmic reticulum stress and apoptosis in the process of adipose-derived stromal cells differentiating into astrocytes.Cell adhesion & migration · 2024Article
- Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair.Journal of molecular cell biology · 2024Article
- Sumoylation of methionine adenosyltransferase alpha 1 promotes mitochondrial dysfunction in alcohol-associated liver disease.Hepatology (Baltimore, Md.) · 2024Article
- Targeting paraptosis in cancer: opportunities and challenges.Cancer gene therapy · 2024Review
- Cell death in atherosclerosis.Cell cycle (Georgetown, Tex.) · 2024Review
- Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy.Cell communication and signaling : CCS · 2024Review
- Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies.Antioxidants (Basel, Switzerland) · 2024Review
- Application of calcium overload-based ion interference therapy in tumor treatment: strategies, outcomes, and prospects.Frontiers in pharmacology · 2024Review
- Endoplasmic reticulum stress associated with lead (Pb)-induced olfactory epithelium toxicity in an olfactory dark basal cell line.FEBS open bio · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis is a form of regulated necrosis mediated by the formation of the necrosome, composed of the RIPK1/RIPK3/MLKL complex. Here, we developed a proximity ligation assay (PLA) that allows in situ visualization of necrosomes in necroptotic cells and in vivo. Using PLA assay, we show that necrosomes can be found in close proximity to the endoplasmic reticulum (ER). Furthermore, we show that necroptosis activates ER stress sensors, PERK, IRE1α, and ATF6 in a RIPK1-RIPK3-MLKL axis-dependent manner. Activated MLKL can be translocated to the ER membrane to directly initiate the activation of ER stress signaling. The activation of IRE1α in necroptosis promotes the splicing of XBP1, and the subsequent incorporation of spliced XBP1 messenger RNA (mRNA) into extracellular vesicles (EVs). Finally, we show that unlike that of a conventional ER stress response, necroptosis promotes the activation of unfolded protein response (UPR) sensors without affecting their binding of GRP78. Our study reveals a signaling pathway that links MLKL activation in necroptosis to an unconventional ER stress response.
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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.