RIP3: a molecular switch for necrosis and inflammation.
TLDR
The current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases is reviewed.Abstract:
The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/ necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tightly regulated by phosphorylation, ubiquitination, and caspase-mediated cleavage. These post-translational modifications coordinately regulate the assembly of a macromolecular signaling complex termed the necrosome. Recently, several reports indicate that RIP3 can promote inflammation independent of its pronecrotic activity. Here, we review our current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases.read more
Citations
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Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Tom Vanden Berghe,Andreas Linkermann,Sandrine Jouan-Lanhouet,Henning Walczak,Peter Vandenabeele +4 more
TL;DR: Elucidating how these pathways of regulated necrosis are interconnected at the molecular level should enable this process to be therapeutically targeted.
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Mixed Lineage Kinase Domain-like Protein MLKL Causes Necrotic Membrane Disruption upon Phosphorylation by RIP3
TL;DR: The development of a monoclonal antibody that specifically recognizes phosphorylated MLKL in cells dying of this pathway and in human liver biopsy samples from patients suffering from drug-induced liver injury is reported.
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Glutaminolysis and Transferrin Regulate Ferroptosis.
TL;DR: Inhibition of glutaminolysis, the essential component of ferroptosis, can reduce heart injury triggered by ischemia/reperfusion, suggesting a potential therapeutic approach for treating related diseases.
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Ferroptosis is an autophagic cell death process
TL;DR: It is reported that inhibition of ferritinophagy by blockage of autophagy or knockdown of NCOA4 abrogated the accumulation of ferroptosis-associated cellular labile iron and reactive oxygen species, as well as eventual ferroPTotic cell death.
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Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria (111.33)
Edward A. Miao,Irina A. Leaf,Piper M. Treuting,Dat P. Mao,Anasuya Sarkar,Mark D. Wewers,Alan Aderem +6 more
TL;DR: It is demonstrated that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.
References
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Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis.
TL;DR: This study reports that the death domain kinase RIP, a key component of the TNF signaling complex, was cleaved by Caspase-8 in TNF-induced apoptosis, and demonstrated that the cleavage of RIP resulted in the blockage of T NF-kappaB activation.
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Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis
Claudia Günther,Eva Martini,Nadine Wittkopf,Kerstin Amann,Benno Weigmann,Helmut Neumann,Maximilian J. Waldner,Stephen M. Hedrick,Stefan Tenzer,Markus F. Neurath,Christoph Becker +10 more
TL;DR: A critical function of caspase-8 is demonstrated in regulating intestinal homeostasis and in protecting IECs from TNF-α-induced necroptotic cell death and high levels of RIP3 in human Paneth cells and increased ne croptosis in the terminal ileum of patients with Crohn’s disease are identified, suggesting a potential role of necropsies in the pathogenesis of this disease.
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Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1
TL;DR: The results and the similarities between FADD−/− mice and mice lacking the β-subunit of the IL-2 receptor suggest that there is an unexpected connection between cell proliferation and apoptosis.
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The Ripoptosome, a Signaling Platform that Assembles in Response to Genotoxic Stress and Loss of IAPs
Tencho Tenev,Katiuscia Bianchi,Maurice Darding,Meike Broemer,Claudia Langlais,Fredrik Wallberg,Anna Zachariou,Juanita Lopez,Marion MacFarlane,Kelvin Cain,Pascal Meier +10 more
TL;DR: Ripoptosome as mentioned in this paper contains RIP1, FADD, and caspase-8, and assembles in response to genotoxic stress-induced depletion of XIAP, cIAP1, and CIAP2.
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Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis
TL;DR: The identification of mixed lineage kinase domain-like, MLKL, as a key RIP3 downstream component of TNF-induced necrosis is reported, which suggests thatMLKL functions downstream of RIP1 and RIP3 and is recruited to the necrosome through its interaction with RIP3.