| First Author | Hughes MM | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 1 | Pages | 151-161.e5 |
| PubMed ID | 31577945 | Mgi Jnum | J:288383 |
| Mgi Id | MGI:6432334 | Doi | 10.1016/j.celrep.2019.08.072 |
| Citation | Hughes MM, et al. (2019) Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation. Cell Rep 29(1):151-161.e5 |
| abstractText | 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)-1beta 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. |
