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Int J Biol Sci 2023; 19(15):4931-4947. doi:10.7150/ijbs.86869 This issue Cite

Review

Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease

Haiyang Jiang1, Peizhao Liu2, Jiaqi Kang2, Jie Wu3, Wenbin Gong4, Xuanheng Li2, Yangguang Li2, Juanhan Liu2, Weizhen Li2, Chujun Ni1, Bo Liao2, Xiuwen Wu2✉, Yun Zhao1✉, Jianan Ren1,2✉

1. Department of General Surgery, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing 210000, China.
2. Research Institute of General Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, China.
3. Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
4. Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.

✉ Corresponding authors: Xiuwen Wu, Department of Surgery, Jinling Hospital, 305 East Zhongshan Rd, Nanjing 210002 China. E-mail: wuxiuwenedu.cn; Yun Zhao, Department of General Surgery, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital o More

Citation:
Jiang H, Liu P, Kang J, Wu J, Gong W, Li X, Li Y, Liu J, Li W, Ni C, Liao B, Wu X, Zhao Y, Ren J. Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease. Int J Biol Sci 2023; 19(15):4931-4947. doi:10.7150/ijbs.86869. https://www.ijbs.com/v19p4931.htm
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Abstract

Graphic abstract

Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.

Keywords: gasdermin, alternative splicing, pyroptosis, posttranslational modifications, dynamical regulation

Citation styles

APA
Jiang, H., Liu, P., Kang, J., Wu, J., Gong, W., Li, X., Li, Y., Liu, J., Li, W., Ni, C., Liao, B., Wu, X., Zhao, Y., Ren, J. (2023). Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease. International Journal of Biological Sciences, 19(15), 4931-4947. https://doi.org/10.7150/ijbs.86869.

ACS
Jiang, H.; Liu, P.; Kang, J.; Wu, J.; Gong, W.; Li, X.; Li, Y.; Liu, J.; Li, W.; Ni, C.; Liao, B.; Wu, X.; Zhao, Y.; Ren, J. Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease. Int. J. Biol. Sci. 2023, 19 (15), 4931-4947. DOI: 10.7150/ijbs.86869.

NLM
Jiang H, Liu P, Kang J, Wu J, Gong W, Li X, Li Y, Liu J, Li W, Ni C, Liao B, Wu X, Zhao Y, Ren J. Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease. Int J Biol Sci 2023; 19(15):4931-4947. doi:10.7150/ijbs.86869. https://www.ijbs.com/v19p4931.htm

CSE
Jiang H, Liu P, Kang J, Wu J, Gong W, Li X, Li Y, Liu J, Li W, Ni C, Liao B, Wu X, Zhao Y, Ren J. 2023. Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease. Int J Biol Sci. 19(15):4931-4947.

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