Gasdermin 作为炎症和细胞死亡的进化保守执行者。
Gasdermins as evolutionarily conserved executors of inflammation and cell death.
发表日期：2024 Aug 26
作者：
Kaiwen W Chen, Petr Broz
来源：
NATURE CELL BIOLOGY
摘要：
Gasdermin 是一个成孔蛋白家族，最近作为焦亡的执行者出现，焦亡是一种细胞死亡的裂解形式，由先天免疫系统诱导以根除感染或恶性细胞。哺乳动物gasdermin 包含细胞毒性N 端结构域、柔性接头和C 端阻遏结构域。连接子中的蛋白水解裂解释放细胞毒性结构域，从而使其形成 β-桶膜孔。质膜中gasdermin孔的形成最终导致电化学梯度丧失、细胞死亡和膜破裂。在这里，我们回顾了最近的工作，通过揭示 Gasdermin 的激活机制、调节及其在自身免疫、宿主防御和癌症中的作用，扩大了我们对 Gasdermin 生物学和功能的理解。我们进一步强调了真菌和细菌 Gasdermin 孔的形成，指出细胞死亡诱导的保守机制。© 2024。Springer Nature Limited。
The gasdermins are a family of pore-forming proteins that have recently emerged as executors of pyroptosis, a lytic form of cell death that is induced by the innate immune system to eradicate infected or malignant cells. Mammalian gasdermins comprise a cytotoxic N-terminal domain, a flexible linker and a C-terminal repressor domain. Proteolytic cleavage in the linker releases the cytotoxic domain, thereby allowing it to form β-barrel membrane pores. Formation of gasdermin pores in the plasma membrane eventually leads to a loss of the electrochemical gradient, cell death and membrane rupture. Here we review recent work that has expanded our understanding of gasdermin biology and function in mammals by revealing their activation mechanism, their regulation and their roles in autoimmunity, host defence and cancer. We further highlight fungal and bacterial gasdermin pore formation pointing to a conserved mechanism of cell death induction.© 2024. Springer Nature Limited.