Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA; email:
Annu Rev Immunol. 2020 Apr 26;38:567-595. doi: 10.1146/annurev-immunol-073119-095439. Epub 2020 Feb 4.
Caspases are a family of conserved cysteine proteases that play key roles in programmed cell death and inflammation. In multicellular organisms, caspases are activated via macromolecular signaling complexes that bring inactive procaspases together and promote their proximity-induced autoactivation and proteolytic processing. Activation of caspases ultimately results in programmed execution of cell death, and the nature of this cell death is determined by the specific caspases involved. Pioneering new research has unraveled distinct roles and cross talk of caspases in the regulation of programmed cell death, inflammation, and innate immune responses. In-depth understanding of these mechanisms is essential to foster the development of precise therapeutic targets to treat autoinflammatory disorders, infectious diseases, and cancer. This review focuses on mechanisms governing caspase activation and programmed cell death with special emphasis on the recent progress in caspase cross talk and caspase-driven gasdermin D-induced pyroptosis.
Caspases 是一组保守的半胱氨酸蛋白酶家族，在程序性细胞死亡和炎症中发挥关键作用。在多细胞生物中，Caspases 通过将无活性的 procaspases 聚集在一起并促进它们的临近诱导自动激活和蛋白水解处理的大分子信号复合物被激活。Caspases 的激活最终导致程序性细胞死亡的执行，并且这种细胞死亡的性质由涉及的特定 Caspases 决定。开创性的新研究揭示了 Caspases 在程序性细胞死亡、炎症和先天免疫反应的调节中的不同作用和串扰。深入了解这些机制对于促进精确治疗靶点的发展以治疗自身炎症性疾病、传染病和癌症至关重要。本综述重点介绍了 Caspases 激活和程序性细胞死亡的调控机制，特别强调了 Caspases 串扰和 Caspases 驱动的 Gasdermin D 诱导的细胞焦亡方面的最新进展。
