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Initiation and execution mechanisms of necroptosis : an overview

Sasker Grootjans (UGent) , Tom Vanden Berghe (UGent) and Peter Vandenabeele (UGent)
(2017) CELL DEATH AND DIFFERENTIATION. 24(7). p.1184-1195
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Abstract
Necroptosis is a form of regulated cell death, which is induced by ligand binding to TNF family death domain receptors, pattern recognizing receptors and virus sensors. The common feature of these receptor systems is the implication of proteins, which contain a receptor interaction protein kinase (RIPK) homology interaction motif (RHIM) mediating recruitment and activation of receptor-interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis executioner mixed lineage kinase domainlike (MLKL). In case of the TNF family members, the initiator is the survival-and cell death-regulating RIPK1 kinase, in the case of Toll-like receptor 3/4 (TLR3/4), a RHIM-containing adaptor, called TRIF, while in the case of Z-DNA-binding protein ZBP1/DAI, the cytosolic viral sensor itself contains a RHIM domain. In this review, we discuss the different protein complexes that serve as nucleation platforms for necroptosis and the mechanism of execution of necroptosis. Transgenic models (knockout, kinase-dead knock-in) and pharmacologic inhibition indicate that RIPK1, RIPK3 or MLKL are implicated in many inflammatory, degenerative and infectious diseases. However, the conclusion of necroptosis being solely involved in the etiology of diseases is blurred by the pleiotropic roles of RIPK1 and RIPK3 in other cellular processes such as apoptosis and inflammasome activation.
Keywords
MIXED LINEAGE KINASE, TUMOR-NECROSIS-FACTOR, DOMAIN-LIKE PROTEIN, NF-KAPPA-B, NECROTIC CELL-DEATH, HOMOTYPIC INTERACTION MOTIF, EXPERIMENTAL DISEASE-MODELS, TNF-INDUCED NECROPTOSIS, NLRP3 INFLAMMASOME, ACTIVATION, PROGRAMMED NECROSIS

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Citation

Please use this url to cite or link to this publication:

Chicago
Grootjans, Sasker, Tom Vanden Berghe, and Peter Vandenabeele. 2017. “Initiation and Execution Mechanisms of Necroptosis : an Overview.” Cell Death and Differentiation 24 (7): 1184–1195.
APA
Grootjans, S., Vanden Berghe, T., & Vandenabeele, P. (2017). Initiation and execution mechanisms of necroptosis : an overview. CELL DEATH AND DIFFERENTIATION, 24(7), 1184–1195.
Vancouver
1.
Grootjans S, Vanden Berghe T, Vandenabeele P. Initiation and execution mechanisms of necroptosis : an overview. CELL DEATH AND DIFFERENTIATION. 2017;24(7):1184–95.
MLA
Grootjans, Sasker, Tom Vanden Berghe, and Peter Vandenabeele. “Initiation and Execution Mechanisms of Necroptosis : an Overview.” CELL DEATH AND DIFFERENTIATION 24.7 (2017): 1184–1195. Print.
@article{8527468,
  abstract     = {Necroptosis is a form of regulated cell death, which is induced by ligand binding to TNF family death domain receptors, pattern recognizing receptors and virus sensors. The common feature of these receptor systems is the implication of proteins, which contain a receptor interaction protein kinase (RIPK) homology interaction motif (RHIM) mediating recruitment and activation of receptor-interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis executioner mixed lineage kinase domainlike (MLKL). In case of the TNF family members, the initiator is the survival-and cell death-regulating RIPK1 kinase, in the case of Toll-like receptor 3/4 (TLR3/4), a RHIM-containing adaptor, called TRIF, while in the case of Z-DNA-binding protein ZBP1/DAI, the cytosolic viral sensor itself contains a RHIM domain. In this review, we discuss the different protein complexes that serve as nucleation platforms for necroptosis and the mechanism of execution of necroptosis. Transgenic models (knockout, kinase-dead knock-in) and pharmacologic inhibition indicate that RIPK1, RIPK3 or MLKL are implicated in many inflammatory, degenerative and infectious diseases. However, the conclusion of necroptosis being solely involved in the etiology of diseases is blurred by the pleiotropic roles of RIPK1 and RIPK3 in other cellular processes such as apoptosis and inflammasome activation.},
  author       = {Grootjans, Sasker and Vanden Berghe, Tom and Vandenabeele, Peter},
  issn         = {1350-9047},
  journal      = {CELL DEATH AND DIFFERENTIATION},
  keyword      = {MIXED LINEAGE KINASE,TUMOR-NECROSIS-FACTOR,DOMAIN-LIKE PROTEIN,NF-KAPPA-B,NECROTIC CELL-DEATH,HOMOTYPIC INTERACTION MOTIF,EXPERIMENTAL DISEASE-MODELS,TNF-INDUCED NECROPTOSIS,NLRP3 INFLAMMASOME,ACTIVATION,PROGRAMMED NECROSIS},
  language     = {eng},
  number       = {7},
  pages        = {1184--1195},
  title        = {Initiation and execution mechanisms of necroptosis : an overview},
  url          = {http://dx.doi.org/10.1038/cdd.2017.65},
  volume       = {24},
  year         = {2017},
}

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