Z-DNA binding protein 1 promotes heatstroke-induced cell death.

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-

Heat Stroke* ; Nucleic Acids*; Cell Death ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics

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.

0 (DNA-Binding Proteins)
0 (Nucleic Acids)
0 (RNA-Binding Proteins)
0 (ZBP1 protein, human)
EC 2.7.11.1 (RIPK3 protein, human)
EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)

Date Created: 20220505 Date Completed: 20220509 Latest Revision: 20220531

20231215

10.1126/science.abg5251

35511979