Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation
Item Type:Journal Article
Citation:Hughes, M.M., Hooftman, A., Angiari, S., Tummala, P., Zaslona, Z., Runtsch, M.C., McGettrick, A.F., Sutton, C.E., Diskin, C., Rooke, M., Takahashi, S., Sundararaj, S., Casarotto, M.G., Dahlstrom, J.E., Palsson-McDermott, E.M., Corr, S.C., Mills, K.H.G., Preston, R.J.S., Neamati, N., Xie, Y., Baell, J.B., Board, P.G., O'Neill, L.A.J., Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation, Cell Reports, 2019, Oct 1;29(1):151-161.e5.
1-s2.0-S2211124719311271-main.pdf (Published (author's copy) - Peer Reviewed) 3.318Mb
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.
Science Foundation Ireland
Type of material:Journal Article
Series/Report no:Cell Reports;
Availability:Full text available
Keywords:glutathione transferase omega 1-1 (GSTO1-1), NLRP3 activation, pro-inflammatory cytokines interleukin-1 beta (IL)-1β, GSTO1-1, IL-1β, NEK7, NLRP3 inflammasome, Deglutathionylation, Glutathione, Pyroptosis