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  5. Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation

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Article
English
2019

Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation

0 Datasets

0 Files

English
2019
Cell Reports
Vol 29 (1)
DOI: 10.1016/j.celrep.2019.08.072

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Luke O'neill
Luke O'neill

Trinity College Dublin

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Mark Hughes
Alexander Hooftman
Stefano Angiari
+20 more

Abstract

The NLRP3 inflammasome is a cytosolic complex sensing phagocytosed material and various damage-associated molecular patterns, triggering production of the pro-inflammatory cytokines interleukin-1 beta (IL)-1β and IL-18 and promoting pyroptosis. Here, we characterize glutathione transferase omega 1-1 (GSTO1-1), a constitutive deglutathionylating enzyme, as a regulator of the NLRP3 inflammasome. Using a small molecule inhibitor of GSTO1-1 termed C1-27, endogenous GSTO1-1 knockdown, and GSTO1-1-/- mice, we report that GSTO1-1 is involved in NLRP3 inflammasome activation. Mechanistically, GSTO1-1 deglutathionylates cysteine 253 in NIMA related kinase 7 (NEK7) to promote NLRP3 activation. We therefore identify GSTO1-1 as an NLRP3 inflammasome regulator, which has potential as a drug target to limit NLRP3-mediated inflammation.

How to cite this publication

Mark Hughes, Alexander Hooftman, Stefano Angiari, Padmaja Tummala, Zbigniew Zasłona, Marah C. Runtsch, Anne F. McGettrick, Caroline E. Sutton, Ciana Diskin, Melissa Rooke, Shuhei Takahashi, Srinivasan Sundararaj, Marco G. Casarotto, Jane E. Dahlstrom, Eva M. Pålsson‐McDermott, Sinéad C. Corr, Kingston H. G. Mills, Roger J. S. Preston, Nouri Neamati, Yiyue Xie, Jonathan B. Baell, Philip G. Board, Luke O'neill (2019). Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation. Cell Reports, 29(1), pp. 151-161.e5, DOI: 10.1016/j.celrep.2019.08.072.

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Publication Details

Type

Article

Year

2019

Authors

23

Datasets

0

Total Files

0

Language

English

Journal

Cell Reports

DOI

10.1016/j.celrep.2019.08.072

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