规范的细胞应激颗粒对于砷诱导的由 Z-DNA 结合蛋白 1 介导的细胞坏死至关重要。
Canonical cellular stress granules are required for arsenite-induced necroptosis mediated by Z-DNA-binding protein 1.
机构信息
Biodesign Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, AZ 85281, USA.
College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA.
出版信息
Sci Signal. 2023 Mar 14;16(776):eabq0837. doi: 10.1126/scisignal.abq0837.
Cellular stress granules arise in cells subjected to stress and promote cell survival. A cellular protein that localizes to stress granules is Z-DNA-binding protein 1 (ZBP1), which plays a major role in necroptosis, a programmed cell death pathway mediated by the kinase RIPK3. Here, we showed that the stress granule inducer arsenite activated RIPK3-dependent necroptosis. This pathway required ZBP1, which localized to arsenite-induced stress granules. RIPK3 localized to stress granules in the presence of ZBP1, leading to the formation of ZBP1-RIPK3 necrosomes, phosphorylation of the RIPK3 effector MLKL, and execution of necroptosis. Cells that did not form stress granules did not induce necroptosis in response to arsenite. Together, these results show that arsenite induces ZBP1-mediated necroptosis in a manner dependent on stress granule formation.
细胞应激颗粒出现在受到应激的细胞中，并促进细胞存活。一种定位于应激颗粒的细胞蛋白是 Z-DNA 结合蛋白 1（ZBP1），它在由激酶 RIPK3 介导的程序性细胞死亡途径坏死性凋亡中起主要作用。在这里，我们表明应激颗粒诱导剂亚砷酸盐激活了依赖于 RIPK3 的细胞坏死。该途径需要定位于亚砷酸盐诱导的应激颗粒中的 ZBP1。在存在 ZBP1 的情况下，RIPK3 定位于应激颗粒中，导致 ZBP1-RIPK3 坏死小体的形成、RIPK3 效应物 MLKL 的磷酸化以及细胞坏死的发生。未形成应激颗粒的细胞不会响应亚砷酸盐诱导细胞坏死。总之，这些结果表明亚砷酸盐以依赖于应激颗粒形成的方式诱导 ZBP1 介导的细胞坏死。
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