Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis

  title={Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis},
  author={Kim Newton and Debra L. Dugger and Katherine E. Wickliffe and Neeraj Kapoor and M. Cristina de Almagro and Domagoj Vucic and L{\'a}szl{\'o} G. Kőműves and Ronald E. Ferrando and Dorothy M. French and Joshua Webster and Merone Roose-Girma and S\oren Warming and Vishva M. Dixit},
Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 trigger pro-inflammatory cell death termed “necroptosis.” Studies with RIPK3-deficient mice or the RIPK1 inhibitor necrostatin-1 suggest that necroptosis exacerbates pathology in many disease models. We engineered mice expressing catalytically inactive RIPK3 D161N or RIPK1 D138N to determine the need for the active kinase in the whole animal. Unexpectedly, RIPK3 D161N promoted lethal RIPK1- and caspase-8–dependent apoptosis. In contrast… CONTINUE READING
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  • Y. H. Park, M. S. Jeong, H. H. Park, S. B. Jang
  • Biophys. Acta
  • 1834
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