Z-DNA binding protein 1 promotes heatstroke-induced cell death
- 6 May 2022
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 376 (6593), 609-615
- https://doi.org/10.1126/science.abg5251
Abstract
Heatstroke is a heat stress–induced, life-threatening condition associated with circulatory failure and multiple organ dysfunctions. If global warming continues, heatstroke might become a more prominent cause of mortality worldwide, but its pathogenic mechanism is not well understood. We found that Z-DNA binding protein 1 (ZBP1), a Z–nucleic acid receptor, mediated heatstroke by triggering receptor-interacting protein kinase 3 (RIPK3)–dependent cell death. Heat stress increased the expression of ZBP1 through heat shock transcription factor 1 (HSF1) and activated ZBP1 through a mechanism independent of the nucleic acid sensing action. Deletion of ZBP1, RIPK3, or both mixed lineage kinase domain-like (MLKL) and caspase-8 decreased heat stress–induced circulatory failure, organ injury, and lethality. Thus, ZBP1 appears to have a second function that orchestrates host responses to heat stress.This publication has 30 references indexed in Scilit:
- HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell deathCell Death & Disease, 2016
- Caspase-11 cleaves gasdermin D for non-canonical inflammasome signallingNature, 2015
- Cause-Specific Risk of Hospital Admission Related to Extreme Heat in Older AdultsJAMA, 2014
- Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or ApoptosisScience, 2014
- Nanoporous BiVO 4 Photoanodes with Dual-Layer Oxygen Evolution Catalysts for Solar Water SplittingScience, 2014
- Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell deathCell Research, 2013
- Small heat-shock proteins protect from heat-stroke-associated neurodegenerationNature, 2012
- DAI/ZBP1/DLM-1 Complexes with RIP3 to Mediate Virus-Induced Programmed Necrosis that Is Targeted by Murine Cytomegalovirus vIRACell Host & Microbe, 2012
- Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 KinaseCell, 2012
- Disseminated Intravascular CoagulationThe New England Journal of Medicine, 1999