ZBP1 orchestrates dynamic transitions between cell death pathways in response to arsenic and hyperosmotic stress.

ABSTRACT: Z-DNA binding protein 1 (ZBP1), a sensor of Z-form nucleic acids, plays a crucial role in cell death and inflammation. While its functions in infection and development are well-established, its involvement in environmental stress responses remains largely unexplored. In this study, we uncovered novel mechanisms by which ZBP1 mediates cell death under arsenic and hyperosmotic stress. We demonstrate that ZBP1 initiates necroptosis during the early stages of these stresses. As the stress persists, the cell death mode evolves, shifting towards apoptosis and pyroptosis in later stages. This transition is particularly pronounced when the necroptotic pathway is compromised. Interestingly, despite previous implications of stress granules (SGs) in arsenic-dependent cell death, we found that neither

SUBMITTER: Fu Y 

PROVIDER: S-EPMC12666829 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature