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The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis.
Onizawa, Michio; Oshima, Shigeru; Schulze-Topphoff, Ulf; Oses-Prieto, Juan A; Lu, Timothy; Tavares, Rita; Prodhomme, Thomas; Duong, Bao; Whang, Michael I; Advincula, Rommel; Agelidis, Alex; Barrera, Julio; Wu, Hao; Burlingame, Alma; Malynn, Barbara A; Zamvil, Scott S; Ma, Averil.
Afiliação
  • Onizawa M; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Oshima S; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Schulze-Topphoff U; Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
  • Oses-Prieto JA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
  • Lu T; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Tavares R; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Prodhomme T; Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
  • Duong B; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Whang MI; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Advincula R; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Agelidis A; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Barrera J; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Wu H; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
  • Burlingame A; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
  • Malynn BA; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Zamvil SS; Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
  • Ma A; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Nat Immunol ; 16(6): 618-27, 2015 Jun.
Article em En | MEDLINE | ID: mdl-25939025
A20 is an anti-inflammatory protein linked to multiple human diseases; however, the mechanisms by which A20 prevents inflammatory disease are incompletely defined. We found that A20-deficient T cells and fibroblasts were susceptible to caspase-independent and kinase RIPK3-dependent necroptosis. Global deficiency in RIPK3 significantly restored the survival of A20-deficient mice. A20-deficient cells exhibited exaggerated formation of RIPK1-RIPK3 complexes. RIPK3 underwent physiological ubiquitination at Lys5 (K5), and this ubiquitination event supported the formation of RIPK1-RIPK3 complexes. Both the ubiquitination of RIPK3 and formation of the RIPK1-RIPK3 complex required the catalytic cysteine of A20's deubiquitinating motif. Our studies link A20 and the ubiquitination of RIPK3 to necroptotic cell death and suggest additional mechanisms by which A20 might prevent inflammatory disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cisteína Endopeptidases / Linfócitos T / Peptídeos e Proteínas de Sinalização Intracelular / Proteína Serina-Treonina Quinases de Interação com Receptores / Fibroblastos Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cisteína Endopeptidases / Linfócitos T / Peptídeos e Proteínas de Sinalização Intracelular / Proteína Serina-Treonina Quinases de Interação com Receptores / Fibroblastos Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article