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Comment
. 2019 May 15;38(10):e102065.
doi: 10.15252/embj.2019102065. Epub 2019 Apr 15.

Chopping GSDMD: caspase-8 has joined the team of pyroptosis-mediating caspases

Anna M Gram  1 , Lee M Booty  1 , Clare E Bryant  1   2
Affiliations
Comment

Chopping GSDMD: caspase-8 has joined the team of pyroptosis-mediating caspases

Anna M Gram et al. EMBO J. .

Abstract

nflammatory and apoptotic caspases mediate two distinct forms of cell death: pyroptosis and apoptosis, respectively. Three independent studies have now demonstrated that the “apoptotic” caspase‐8 can cleave gasdermin D (GSDMD) leading to pyroptosis‐like cell death and IL‐1β release in murine macrophages (Orning et al, 2018; Sarhan et al, 2018; Chen et al, 2019). Orning et al and Chen/Demarco et al also show that the NLRP3 inflammasome is activated downstream of active caspase‐8, but they attribute this inflammasome activation to different pore‐forming proteins, GSDMD and pannexin‐1, respectively (Orning et al, 2018; Chen et al, 2019).

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Figures

Figure 1
Figure 1. Mechanisms of cell death: the connections between caspases and gasdermin D
See this image and copyright information in PMC

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References

    1. Chauhan D, Bartok E, Gaidt MM, Bock FJ, Herrmann J, Seeger JM, Broz P, Beckmann R, Kashkar H, Tait SWG et al (2018) BAX/BAK‐induced apoptosis results in Caspase‐8‐dependent IL‐1beta maturation in macrophages. Cell Rep 25: 2354–2368. e2355 - PubMed
    1. Chen KW, Demarco B, Heilig R, Shkarina K, Boettcher A, Farady CJ, Pelczar P, Broz P (2019) Extrinsic and intrinsic apoptosis activate pannexin‐1 to drive NLRP3 inflammasome assembly. EMBO J 38: e101638 - PMC - PubMed
    1. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25: 486–541 - PMC - PubMed
    1. Lawlor KE, Khan N, Mildenhall A, Gerlic M, Croker BA, D'Cruz AA, Hall C, Kaur Spall S, Anderton H, Masters SL et al (2015) RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat Commun 6: 6282 - PMC - PubMed
    1. Lawlor KE, Feltham R, Yabal M, Conos SA, Chen KW, Ziehe S, Grass C, Zhan Y, Nguyen TA, Hall C et al (2017) XIAP loss triggers RIPK3‐ and Caspase‐8‐driven IL‐1beta activation and cell death as a consequence of TLR‐MyD88‐induced cIAP1‐TRAF2 degradation. Cell Rep 20: 668–682 - PubMed

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