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Mechanisms of Gasdermin Family Members in Inflammasome Signaling and Cell Death

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Feng, Shouya, Fox, Daniel, Man, Si Ming·2018·Journal of Molecular Biology

Abstract

The Gasdermin (GSDM) family consists of Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME) and Pejvakin (PJVK). GSDMD is activated by inflammasome-associated inflammatory caspases. Cleavage of GSDMD by human or mouse caspase-1, human caspase-4, human caspase-5, and mouse caspase-11 liberates the N-terminal effector domain from the C-terminal inhibitory domain. The N-terminal domain oligomerizes in the cell membrane and forms a pore of 10-16 nm in diameter, through which substrates of a smaller diameter, such as interleukin-1β and interleukin-18, are secreted. The increasing abundance of membrane pores ultimately leads to membrane rupture and pyroptosis, releasing the entire cellular content. Other than GSDMD, the N-terminal domain of all GSDMs, with the exception of PJVK, have the ability to form pores. There is evidence to suggest that GSDMB and GSDME are cleaved by apoptotic caspases. Here, we review the mechanistic functions of GSDM proteins with respect to their expression and signaling profile in the cell, with more focused discussions on inflammasome activation and cell death.

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Metadata

Authors
Feng, S., Fox, D., & Man, S. M.
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2018-09
Volume
430
Issue
18
Pages
3068-3080
ISSN
0022-2836 (ISSN-L)
OpenAlex
W2818139375
Cited by
353
References
21
FWCI
10.44
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Mechanisms of Gasdermin Family Members in Inflammasome Signaling and Cell Death. https://app.cochat.ai/papers/10.1016/j.jmb.2018.07.002
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Feng, S., Fox, D., & Man, S. M. (2018). Mechanisms of Gasdermin Family Members in Inflammasome Signaling and Cell Death. Journal of Molecular Biology. https://doi.org/10.1016/j.jmb.2018.07.002

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