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Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation.
Hughes, Mark M; Hooftman, Alexander; Angiari, Stefano; Tummala, Padmaja; Zaslona, Zbigniew; Runtsch, Marah C; McGettrick, Anne F; Sutton, Caroline E; Diskin, Ciana; Rooke, Melissa; Takahashi, Shuhei; Sundararaj, Srinivasan; Casarotto, Marco G; Dahlstrom, Jane E; Palsson-McDermott, Eva M; Corr, Sinead C; Mills, Kingston H G; Preston, Roger J S; Neamati, Nouri; Xie, Yiyue; Baell, Jonathan B; Board, Philip G; O'Neill, Luke A J.
Afiliação
  • Hughes MM; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
  • Hooftman A; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Angiari S; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Tummala P; John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
  • Zaslona Z; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Runtsch MC; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • McGettrick AF; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Sutton CE; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Diskin C; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Rooke M; John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
  • Takahashi S; Department of Human Pathology, Graduate School and Faculty of Medicine, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
  • Sundararaj S; John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
  • Casarotto MG; John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
  • Dahlstrom JE; ACT Pathology and ANU Medical School, The Canberra Hospital, Canberra, ACT, Australia.
  • Palsson-McDermott EM; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Corr SC; Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland.
  • Mills KHG; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • Preston RJS; Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
  • Neamati N; Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA; Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, 2800 Plymouth Road, Building 520, Room 1363, Ann Arbor, MI 481
  • Xie Y; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
  • Baell JB; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
  • Board PG; John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
  • O'Neill LAJ; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. Electronic address: laoneill@tcd.ie.
Cell Rep ; 29(1): 151-161.e5, 2019 10 01.
Article em En | MEDLINE | ID: mdl-31577945
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)-1ß 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inflamassomos / Quinases Relacionadas a NIMA / Proteína 3 que Contém Domínio de Pirina da Família NLR / Glutationa Transferase Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inflamassomos / Quinases Relacionadas a NIMA / Proteína 3 que Contém Domínio de Pirina da Família NLR / Glutationa Transferase Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article