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MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death

Yves Dondelinger (UGent) , Tom Delanghe (UGent) , Diego Rojas Rivera (UGent) , Dario Priem (UGent) , Tinneke Delvaeye (UGent) , Inge Bruggeman (UGent) , Franky Van Herreweghe (UGent) , Peter Vandenabeele (UGent) and Mathieu Bertrand (UGent)
(2017) NATURE CELL BIOLOGY. 19(10). p.1237-1247
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Abstract
TNF is a master proinflammatory cytokine whose pathogenic role in inflammatory disorders can, in certain conditions, be attributed to RIPK1 kinase-dependent cell death. Survival, however, is the default response of most cells to TNF stimulation, indicating that cell demise is normally actively repressed and that specific checkpoints must be turned off for cell death to proceed. We identified RIPK1 as a direct substrate of MK2 in the TNFR1 signalling pathway. Phosphorylation of RIPK1 by MK2 limits cytosolic activation of RIPK1 and the subsequent assembly of the death complex that drives RIPK1 kinase-dependent apoptosis and necroptosis. In line with these in vitro findings, MK2 inactivation greatly sensitizes mice to the cytotoxic effects of TNF in an acute model of sterile shock caused by RIPK1-dependent cell death. In conclusion, we identified MK2-mediated RIPK1 phosphorylation as an important molecular mechanism limiting the sensitivity of the cells to the cytotoxic effects of TNF.
Keywords
NF-KAPPA-B, LINEAR UBIQUITIN, SIGNALING COMPLEXES, INDUCED APOPTOSIS, NUCLEAR EXPORT, KINASE, ACTIVATION, ALPHA, INFLAMMATION, NECROSIS

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MLA
Dondelinger, Yves et al. “MK2 Phosphorylation of RIPK1 Regulates TNF-mediated Cell Death.” NATURE CELL BIOLOGY 19.10 (2017): 1237–1247. Print.
APA
Dondelinger, Y., Delanghe, T., Rojas Rivera, D., Priem, D., Delvaeye, T., Bruggeman, I., Van Herreweghe, F., et al. (2017). MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. NATURE CELL BIOLOGY, 19(10), 1237–1247.
Chicago author-date
Dondelinger, Yves, Tom Delanghe, Diego Rojas Rivera, Dario Priem, Tinneke Delvaeye, Inge Bruggeman, Franky Van Herreweghe, Peter Vandenabeele, and Mathieu Bertrand. 2017. “MK2 Phosphorylation of RIPK1 Regulates TNF-mediated Cell Death.” Nature Cell Biology 19 (10): 1237–1247.
Chicago author-date (all authors)
Dondelinger, Yves, Tom Delanghe, Diego Rojas Rivera, Dario Priem, Tinneke Delvaeye, Inge Bruggeman, Franky Van Herreweghe, Peter Vandenabeele, and Mathieu Bertrand. 2017. “MK2 Phosphorylation of RIPK1 Regulates TNF-mediated Cell Death.” Nature Cell Biology 19 (10): 1237–1247.
Vancouver
1.
Dondelinger Y, Delanghe T, Rojas Rivera D, Priem D, Delvaeye T, Bruggeman I, et al. MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. NATURE CELL BIOLOGY. 2017;19(10):1237–47.
IEEE
[1]
Y. Dondelinger et al., “MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death,” NATURE CELL BIOLOGY, vol. 19, no. 10, pp. 1237–1247, 2017.
@article{8537849,
  abstract     = {TNF is a master proinflammatory cytokine whose pathogenic role in inflammatory disorders can, in certain conditions, be attributed to RIPK1 kinase-dependent cell death. Survival, however, is the default response of most cells to TNF stimulation, indicating that cell demise is normally actively repressed and that specific checkpoints must be turned off for cell death to proceed. We identified RIPK1 as a direct substrate of MK2 in the TNFR1 signalling pathway. Phosphorylation of RIPK1 by MK2 limits cytosolic activation of RIPK1 and the subsequent assembly of the death complex that drives RIPK1 kinase-dependent apoptosis and necroptosis. In line with these in vitro findings, MK2 inactivation greatly sensitizes mice to the cytotoxic effects of TNF in an acute model of sterile shock caused by RIPK1-dependent cell death. In conclusion, we identified MK2-mediated RIPK1 phosphorylation as an important molecular mechanism limiting the sensitivity of the cells to the cytotoxic effects of TNF.},
  author       = {Dondelinger, Yves and Delanghe, Tom and Rojas Rivera, Diego and Priem, Dario and Delvaeye, Tinneke and Bruggeman, Inge and Van Herreweghe, Franky and Vandenabeele, Peter and Bertrand, Mathieu},
  issn         = {1465-7392},
  journal      = {NATURE CELL BIOLOGY},
  keywords     = {NF-KAPPA-B,LINEAR UBIQUITIN,SIGNALING COMPLEXES,INDUCED APOPTOSIS,NUCLEAR EXPORT,KINASE,ACTIVATION,ALPHA,INFLAMMATION,NECROSIS},
  language     = {eng},
  number       = {10},
  pages        = {1237--1247},
  title        = {MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death},
  url          = {http://dx.doi.org/10.1038/ncb3608},
  volume       = {19},
  year         = {2017},
}

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