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. Author manuscript; available in PMC: 2023 Oct 9.
Published in final edited form as: Sci Signal. 2023 Mar 14;16(776):eabq0837. doi: 10.1126/scisignal.abq0837

Fig. 6. Schematic model of stress-granule mediated necroptosis.

Fig. 6.

(A) In cells treated with arsenite, the formation of stress granules is induced. Stress granules are formed as result of HRI-mediated integrated stress response (4). When stress granules are formed, ZBP1 localizes to stress granules, where it is likely to bind to Z-RNA (34, 40, 41). Binding to Z-RNA may result in a conformational change in ZBP1, exposing its RHIM. ZBP1 in stress granules recruits RIPK3 by RHIM-RHIM interactions and the two proteins will form necrosomes, leading to the execution of necroptosis. Red arrows indicate translocation of proteins. (B) When formation of stress granules is inhibited, whether chemically (CHX, ISRIB) or genetically (Tia1−/−, G3bp1/2−/−), ZBP1 remains localized in the cytoplasm and is unable to form necrosomes. Necroptosis is not activated.