通过对gasdermin D进行翻译后修饰来控制细胞焦亡

Controlling pyroptosis through post-translational modifications of gasdermin D.

作者信息

Zhang Na, Xu Daichao

机构信息

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China; Shanghai Key Laboratory of Aging Studies, Shanghai 201210, China; Shanghai Academy of Natural Sciences (SANS), Fudan University, Shanghai 200031, China.

出版信息

Dev Cell. 2025 Apr 7;60(7):994-1007. doi: 10.1016/j.devcel.2025.02.005.

DOI:10.1016/j.devcel.2025.02.005

PMID:40199241

Abstract

Pyroptosis, a lytic and programmed cell death pathway, is mediated by gasdermins (GSDMs), with GSDMD playing an important role in innate immunity and pathology. Upon activation, GSDMD is cleaved to release the active N-terminal fragment that oligomerizes into membrane pores, which promote pyroptosis and cytokine secretion, leading to inflammation. Emerging evidence indicates that post-translational modification (PTM) is an important regulatory mechanism of GSDMD activity. This review explores how PTMs, aside from proteolytic cleavage, control GSDMD activity and link biological contexts to pyroptosis in innate immunity and inflammation, which could inform future studies and therapeutic solutions for treating inflammatory conditions.

摘要

细胞焦亡是一种溶解性程序性细胞死亡途径，由gasdermin（GSDM）介导，其中GSDMD在固有免疫和病理学中发挥重要作用。激活后，GSDMD被切割以释放活性N端片段，该片段寡聚形成膜孔，促进细胞焦亡和细胞因子分泌，从而导致炎症。新出现的证据表明，翻译后修饰（PTM）是GSDMD活性的重要调节机制。本综述探讨了除蛋白水解切割外，PTM如何控制GSDMD活性，并将生物学背景与固有免疫和炎症中的细胞焦亡联系起来，这可为未来治疗炎症性疾病的研究和治疗方案提供参考。