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Ubiquitin-Mediated Regulation of RIPK1 Kinase Activity Independent of IKK and MK2.
Annibaldi, Alessandro; Wicky John, Sidonie; Vanden Berghe, Tom; Swatek, Kirby N; Ruan, Jianbin; Liccardi, Gianmaria; Bianchi, Katiuscia; Elliott, Paul R; Choi, Sze Men; Van Coillie, Samya; Bertin, John; Wu, Hao; Komander, David; Vandenabeele, Peter; Silke, John; Meier, Pascal.
Afiliação
  • Annibaldi A; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK. Electronic address: alessandro.annibaldi@icr.ac.uk.
  • Wicky John S; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
  • Vanden Berghe T; VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  • Swatek KN; Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.
  • Ruan J; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Room 3024B, 3 Blackfan Circle, Boston, MA 02115, USA.
  • Liccardi G; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
  • Bianchi K; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK; Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
  • Elliott PR; Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.
  • Choi SM; VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  • Van Coillie S; VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  • Bertin J; Pattern Recognition Receptor DPU and Platform Technology and Science, GlaxoSmithKline, Collegeville Road, Collegeville, PA 19426, USA.
  • Wu H; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Room 3024B, 3 Blackfan Circle, Boston, MA 02115, USA.
  • Komander D; Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.
  • Vandenabeele P; VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  • Silke J; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia.
  • Meier P; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK. Electronic address: pmeier@icr.ac.uk.
Mol Cell ; 69(4): 566-580.e5, 2018 02 15.
Article em En | MEDLINE | ID: mdl-29452637
Tumor necrosis factor (TNF) can drive inflammation, cell survival, and death. While ubiquitylation-, phosphorylation-, and nuclear factor κB (NF-κB)-dependent checkpoints suppress the cytotoxic potential of TNF, it remains unclear whether ubiquitylation can directly repress TNF-induced death. Here, we show that ubiquitylation regulates RIPK1's cytotoxic potential not only via activation of downstream kinases and NF-kB transcriptional responses, but also by directly repressing RIPK1 kinase activity via ubiquitin-dependent inactivation. We find that the ubiquitin-associated (UBA) domain of cellular inhibitor of apoptosis (cIAP)1 is required for optimal ubiquitin-lysine occupancy and K48 ubiquitylation of RIPK1. Independently of IKK and MK2, cIAP1-mediated and UBA-assisted ubiquitylation suppresses RIPK1 kinase auto-activation and, in addition, marks it for proteasomal degradation. In the absence of a functional UBA domain of cIAP1, more active RIPK1 kinase accumulates in response to TNF, causing RIPK1 kinase-mediated cell death and systemic inflammatory response syndrome. These results reveal a direct role for cIAP-mediated ubiquitylation in controlling RIPK1 kinase activity and preventing TNF-mediated cytotoxicity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Serina-Treonina Quinases / MAP Quinase Quinase Quinases / Ubiquitina / Peptídeos e Proteínas de Sinalização Intracelular / Quinase I-kappa B / Proteínas Inibidoras de Apoptose / Proteína Serina-Treonina Quinases de Interação com Receptores / Proteína 3 com Repetições IAP de Baculovírus Limite: Animals / Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Serina-Treonina Quinases / MAP Quinase Quinase Quinases / Ubiquitina / Peptídeos e Proteínas de Sinalização Intracelular / Quinase I-kappa B / Proteínas Inibidoras de Apoptose / Proteína Serina-Treonina Quinases de Interação com Receptores / Proteína 3 com Repetições IAP de Baculovírus Limite: Animals / Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2018 Tipo de documento: Article