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An outline of necrosome triggers

(2016) CELLULAR AND MOLECULAR LIFE SCIENCES. 73(11-12). p.2137-2152
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Abstract
Necroptosis was initially identified as a backup cell death program when apoptosis is blocked. However, it is now recognized as a cellular defense mechanism against infections and is presumed to be a detrimental factor in several pathologies driven by cell death. Necroptosis is a prototypic form of regulated necrosis that depends on activation of the necrosome, which is a protein complex in which receptor interacting protein kinase (RIPK) 3 is activated. The RIP homotypic interaction motif (RHIM) is the core domain that regulates activation of the necrosome. To date, three RHIM-containing proteins have been reported to activate the kinase activity of RIPK3 within the necrosome: RIPK1, Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF), and DNA-dependent activator of interferon regulatory factors (DAI). Here, we review and discuss commonalities and differences of the increasing number of activators of the necrosome. Since the discovery that activation of mixed lineage kinase domain-like (MLKL) by RIPK3 kinase activity is crucial in necroptosis, interest has increased in monitoring and therapeutically targeting their activation. The availability of new phospho-specific antibodies, pharmacologic inhibitors, and transgenic models will allow us to further document the role of necroptosis in degenerative, inflammatory and infectious diseases.
Keywords
NLRP3 INFLAMMASOME ACTIVATION, MYELOID-LEUKEMIA CELLS, ISCHEMIA-REPERFUSION INJURY, HOMOTYPIC INTERACTION MOTIF, INDUCED LIVER-INJURY, INDUCED CELL-DEATH, TNF-INDUCED NECROPTOSIS, DOMAIN-LIKE PROTEIN, NF-KAPPA-B, MIXED LINEAGE KINASE, Pathogens, RIPK3, MLKL, RHIM, RIPK1, Necroptosis

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Citation

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

Chicago
Vanden Berghe, Tom, Behrouz Hassannia, and Peter Vandenabeele. 2016. “An Outline of Necrosome Triggers.” Cellular and Molecular Life Sciences 73 (11-12): 2137–2152.
APA
Vanden Berghe, T., Hassannia, B., & Vandenabeele, P. (2016). An outline of necrosome triggers. CELLULAR AND MOLECULAR LIFE SCIENCES, 73(11-12), 2137–2152.
Vancouver
1.
Vanden Berghe T, Hassannia B, Vandenabeele P. An outline of necrosome triggers. CELLULAR AND MOLECULAR LIFE SCIENCES. 2016;73(11-12):2137–52.
MLA
Vanden Berghe, Tom, Behrouz Hassannia, and Peter Vandenabeele. “An Outline of Necrosome Triggers.” CELLULAR AND MOLECULAR LIFE SCIENCES 73.11-12 (2016): 2137–2152. Print.
@article{8029070,
  abstract     = {Necroptosis was initially identified as a backup cell death program when apoptosis is blocked. However, it is now recognized as a cellular defense mechanism against infections and is presumed to be a detrimental factor in several pathologies driven by cell death. Necroptosis is a prototypic form of regulated necrosis that depends on activation of the necrosome, which is a protein complex in which receptor interacting protein kinase (RIPK) 3 is activated. The RIP homotypic interaction motif (RHIM) is the core domain that regulates activation of the necrosome. To date, three RHIM-containing proteins have been reported to activate the kinase activity of RIPK3 within the necrosome: RIPK1, Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF), and DNA-dependent activator of interferon regulatory factors (DAI). Here, we review and discuss commonalities and differences of the increasing number of activators of the necrosome. Since the discovery that activation of mixed lineage kinase domain-like (MLKL) by RIPK3 kinase activity is crucial in necroptosis, interest has increased in monitoring and therapeutically targeting their activation. The availability of new phospho-specific antibodies, pharmacologic inhibitors, and transgenic models will allow us to further document the role of necroptosis in degenerative, inflammatory and infectious diseases.},
  author       = {Vanden Berghe, Tom and Hassannia, Behrouz and Vandenabeele, Peter},
  issn         = {1420-682X},
  journal      = {CELLULAR AND MOLECULAR LIFE SCIENCES},
  language     = {eng},
  number       = {11-12},
  pages        = {2137--2152},
  title        = {An outline of necrosome triggers},
  url          = {http://dx.doi.org/10.1007/s00018-016-2189-y},
  volume       = {73},
  year         = {2016},
}

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