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
Kinase RIP3 Is Dispensable for Normal NF-κBs, Signaling by the B-Cell and T-Cell Receptors, Tumor Necrosis Factor Receptor 1, and Toll-Like Receptors 2 and 4
TL;DR: RIP3 is generated by gene targeting and found to be dispensable for normal mouse development, which can exclude RIP3 as an essential modulator of NF-κB signaling downstream of several receptor systems.
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Requirement for Casper (c-FLIP) in Regulation of Death Receptor–Induced Apoptosis and Embryonic Development
Wen-Chen Yeh,Annick Itie,Andrew J. Elia,Michelle Ng,Hong-Bing Shu,Andrew Wakeham,Christine Mirtsos,Nobutaka Suzuki,Madeleine Bonnard,David V. Goeddel,Tak W. Mak +10 more
TL;DR: It is suggested that Casper has two distinct roles: to cooperate with FADD and caspase-8 during embryonic development and to mediate cytoprotection against death factor-induced apoptosis.
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Virus Inhibition of RIP3-Dependent Necrosis
TL;DR: In this article, the authors found that a virus-encoded inhibitor of RIP activation (vIRA) targets RIP3 during infection and disrupts RIP3-RIP1 interactions characteristic of TNFα-induced necroptosis, thereby suppressing both death pathways.
Journal ArticleDOI
RIP Kinase-Dependent Necrosis Drives Lethal Systemic Inflammatory Response Syndrome
Linde Duprez,Nozomi Takahashi,Nozomi Takahashi,Filip Van Hauwermeiren,Filip Van Hauwermeiren,Benjamin Vandendriessche,Benjamin Vandendriessche,Vera Goossens,Vera Goossens,Tom Vanden Berghe,Tom Vanden Berghe,Wim Declercq,Wim Declercq,Claude Libert,Claude Libert,Anje Cauwels,Anje Cauwels,Peter Vandenabeele,Peter Vandenabeele +18 more
TL;DR: It is suggested that RIPK1-RIPK3-mediated cellular damage by necrosis drives mortality during TNF-induced SIRS, and RIPK3 deficiency also protected against cecal ligation and puncture, underscoring the clinical relevance of RIPK kinase inhibition in sepsis.
Journal ArticleDOI
Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity
Leonardo Salmena,Bénédicte Lemmers,Anne Hakem,Elzbieta Matysiak-Zablocki,Kiichi Murakami,P.Y. Billie Au,Donna M Berry,Laura Tamblyn,Amro Shehabeldin,Eva Migon,Andrew Wakeham,Denis Bouchard,Wen Chen Yeh,J McGlade,Pamela S. Ohashi,Razqallah Hakem +15 more
TL;DR: An essential, cell-stage-specific role for caspase 8 in T- cell homeostasis and T-cell-mediated immunity is identified, consistent with the recent identification of caspases 8 mutations in human immunodeficiency.