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
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Glutaminolysis and Transferrin Regulate Ferroptosis.
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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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TNF-α Induces Two Distinct Caspase-8 Activation Pathways
Lai Wang,Fenghe Du,Xiaodong Wang +2 more
TL;DR: It is revealed that TNF-alpha is able to induce apoptosis via two distinct caspase-8 activation pathways that are differentially regulated by cIAP1/2 and c-FLIP.
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Catalytic activity of the caspase-8–FLIP L complex inhibits RIPK3-dependent necrosis
Andrew Oberst,Christopher P. Dillon,Ricardo Weinlich,Laura L. McCormick,Patrick Fitzgerald,Cristina Pop,Razq Hakem,Guy S. Salvesen,Douglas R. Green +8 more
TL;DR: It is found that caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIPL, also known as CFLAR), and this complex is required for the protective function.
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The Death Domain Kinase RIP Mediates the TNF-Induced NF-κB Signal
TL;DR: Sensitivity to TNFalpha-mediated cell death in rip-/- cells is accompanied by a failure to activate the transcription factor NF-kappaB, and the physiologic role(s) that RIP plays in regulating apoptosis in vivo is defined.
Journal ArticleDOI
Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
Edward A. Miao,Irina A. Leaf,Piper M. Treuting,Dat P. Mao,Monica Dors,Anasuya Sarkar,Sarah E. Warren,Sarah E. Warren,Mark D. Wewers,Alan Aderem +9 more
TL;DR: The authors showed 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.
Journal ArticleDOI
Macrophage death and defective inflammation resolution in atherosclerosis.
TL;DR: This Review provides an overview of concepts, with a focus on macrophage death and defective apoptotic cell clearance, and discusses new therapeutic strategies designed to boost inflammation resolution in atherosclerosis.