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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Journal ArticleDOI
Fas-associated death domain (FADD) is a negative regulator of T-cell receptor–mediated necroptosis
Stephanie L. Osborn,Gretchen E. Diehl,Seong-Ji Han,Ling Xue,Nadia S. Kurd,Kristina Hsieh,Dragana Cado,Ellen A. Robey,Astar Winoto +8 more
TL;DR: It is found that programmed necrosis occurs during the late stage of normal T-cell proliferation and that this process is greatly amplified in FADD-deficient T cells, indicating that FADD constitutes a mechanism to keep TCR-induced programmed necrotic signaling in check during early phases of T- cell clonal expansion.
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Dichotomy between RIP1- and RIP3-mediated necroptosis in tumor necrosis factor-α-induced shock.
Andreas Linkermann,Jan Hinrich Bräsen,Federica De Zen,Ricardo Weinlich,Reto A. Schwendener,Douglas R. Green,Ulrich Kunzendorf,Stefan Krautwald +7 more
TL;DR: It is demonstrated that RIP3-deficient mice are protected markedly from TNFα-mediated shock in the presence and absence of caspase inhibition, and it is shown that the fusion protein TAT-crmA, previously demonstrated to inhibit apoptosis, also prevents necroptosis in L929, HT29 and FADD- deficient Jurkat cells.
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Identification of RIP3, a RIP-like kinase that activates apoptosis and NFκB
Pei Wen Yu,Betty Huang,Mary Shen,Jeff Quast,Eva Chan,Xiang Xu,Garry P. Nolan,Donald G. Payan,Ying Luo +8 more
TL;DR: Interestingly, the carboxy-terminal domain of RIP3, like that of RIP, could activate the transcription factor NFκB and induce apoptosis when expressed in mammalian cells, and appears to function as an intermediary in TNFα-induced apoptosis.
Journal ArticleDOI
The RIP-like kinase, RIP3, induces apoptosis and NF-κB nuclear translocation and localizes to mitochondria
TL;DR: Results indicate that rip3 mRNA displays a restricted pattern of expression including regions of the adult central nervous system, and point mutations of RIP3 at amino acids conserved among death domains, abrogated its apoptotic activity.
Journal ArticleDOI
Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity
Jennifer V. Lu,Brian M. Weist,Bram J. van Raam,Brett S. Marro,Long Nguyen,Prathna Srinivas,Bryan D. Bell,Keith A. Luhrs,Thomas E. Lane,Guy S. Salvesen,Craig M. Walsh +10 more
TL;DR: It is demonstrated that RIPK3 and FADD have opposing and complementary roles in promoting T-cell clonal expansion and homeostasis, and caspase-mediated cleavage of RIPK1-containing necrosis inducing complexes (necrosomes) is sufficient to prevent necroptosis in the face of death receptor signaling.