The web of death: the expanding complexity of necroptotic signaling

Innate Sensors Trigger Regulated Cell Death to Combat Intracellular Infection

(2022) Kengo Nozaki et al.   Annual Review of Immunology

Site-specific ubiquitination of MLKL targets it to endosomes and targets Listeria and Yersinia to the lysosomes

(2022) Seongmin Yoon et al.   CELL DEATH AND DIFFERENTIATION

Membrane permeabilization is mediated by distinct epitopes in mouse and human orthologs of the necroptosis effector, MLKL

(2022) Ashish Sethi et al.   CELL DEATH AND DIFFERENTIATION

Mosaic composition of RIP1–RIP3 signalling hub and its role in regulating cell death

(2022) Xin Chen et al.   NATURE CELL BIOLOGY

Z-DNA binding protein 1 promotes heatstroke-induced cell death

(2022) Fangfang Yuan et al.   SCIENCE

Osmotic stress activates RIPK3/MLKL-mediated necroptosis by increasing cytosolic pH through a plasma membrane Na + /H + exchanger

(2022) Wenbin Zhang et al.   Science Signaling

The Lck inhibitor, AMG-47a, blocks necroptosis and implicates RIPK1 in signalling downstream of MLKL

(2022) Annette V. Jacobsen et al.   Cell Death & Disease

The regulation of necroptosis by post-translational modifications

(2021) Yanxiang Meng et al.   CELL DEATH AND DIFFERENTIATION

A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation

(2021) Zhijun Liu et al.   IMMUNITY

RIP1-dependent linear and nonlinear recruitments of caspase-8 and RIP3 respectively to necrosome specify distinct cell death outcomes

(2021) Xiang Li et al.   Protein & Cell

Location, location, location: A compartmentalized view of TNF-induced necroptotic signaling

(2021) André L. Samson et al.   Science Signaling

The amyloid structure of mouse RIPK3 (receptor interacting protein kinase 3) in cell necroptosis

(2021) Xia-lian Wu et al.   Nature Communications

Necroptosis, pyroptosis and apoptosis: an intricate game of cell death

(2021) Damien Bertheloot et al.   Cellular & Molecular Immunology

Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis

(2021) Sarah E. Garnish et al.   Nature Communications

CAMK2/CaMKII activates MLKL in short-term starvation to facilitate autophagic flux

(2021) Qionghui Zhan et al.   Autophagy

Evolutionary Profile for (Host and Viral) MLKL Indicates Its Activities as a Battlefront for Extensive Counteradaptation

(2021) Suzette N Palmer et al.   MOLECULAR BIOLOGY AND EVOLUTION

The Role of the Key Effector of Necroptotic Cell Death, MLKL, in Mouse Models of Disease

(2021) Emma C. Tovey Crutchfield et al.   Biomolecules

A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis

(2021) Kathy Weisel et al.   BMJ Open Gastroenterology

Spontaneous necroptosis and autoinflammation are blocked by an inhibitory phosphorylation on MLKL during neonatal development

(2021) Xinxin Zhu et al.   CELL RESEARCH

XDeathDB: a visualization platform for cell death molecular interactions

(2021) Venkat Sundar Gadepalli et al.   Cell Death & Disease

Quantitative analysis of phosphoproteome in necroptosis reveals a role of TRIM28 phosphorylation in promoting necroptosis-induced cytokine production

(2021) Rui Zu et al.   Cell Death & Disease

Human RIPK3 maintains MLKL in an inactive conformation prior to cell death by necroptosis

(2021) Yanxiang Meng et al.   Nature Communications

Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling

(2021) Maria C. Tanzer et al.   Nature Communications

Constitutive Interferon Attenuates RIPK1/3-Mediated Cytokine Translation

(2020) Hayley I. Muendlein et al.   Cell Reports

Quantitative and Dynamic Catalogs of Proteins Released during Apoptotic and Necroptotic Cell Death

(2020) Maria C. Tanzer et al.   Cell Reports

Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis

(2020) Ting Zhang et al.   CELL

New insights into the regulation of apoptosis, necroptosis, and pyroptosis by receptor interacting protein kinase 1 and caspase-8

(2020) Robin Schwarzer et al.   CURRENT OPINION IN CELL BIOLOGY

MLKL-dependent signaling regulates autophagic flux in a murine model of non-alcohol-associated fatty liver and steatohepatitis

(2020) Xiaoqin Wu et al.   JOURNAL OF HEPATOLOGY

Identification of MLKL membrane translocation as a checkpoint in necroptotic cell death using Monobodies

(2020) Emma J. Petrie et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression

(2020) Jialin Dai et al.   Cell Death & Disease

Comprehensive Map of the Regulated Cell Death Signaling Network: A Powerful Analytical Tool for Studying Diseases

(2020) Jean-Marie Ravel et al.   Cancers

MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis

(2020) Andre L. Samson et al.   Nature Communications

Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues

(2020) Katherine A. Davies et al.   Nature Communications

A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction

(2020) Joanne M. Hildebrand et al.   Nature Communications

Discovery of a Family of Mixed Lineage Kinase Domain-like Proteins in Plants and Their Role in Innate Immune Signaling

(2020) Lisa K. Mahdi et al.   Cell Host & Microbe

A Non-canonical PDK1-RSK Signal Diminishes Pro-caspase-8-Mediated Necroptosis Blockade

(2020) Zhang-Hua Yang et al.   MOLECULAR CELL

Emerging connectivity of programmed cell death pathways and its physiological implications

(2020) Sammy Bedoui et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

An incoherent feedforward loop interprets NFκB/RelA dynamics to determine TNF‐induced necroptosis decisions

(2020) Marie Oliver Metzig et al.   Molecular Systems Biology

The bromodomain protein BRD4 positively regulates necroptosis via modulating MLKL expression

(2019) Yu Xiong et al.   CELL DEATH AND DIFFERENTIATION

The pseudokinase MLKL regulates hepatic insulin sensitivity independently of inflammation

(2019) Haixia Xu et al.   Molecular Metabolism

RIPK1 can mediate apoptosis in addition to necroptosis during embryonic development

(2019) Xuhua Zhang et al.   Cell Death & Disease

O-GlcNAc Transferase Suppresses Inflammation and Necroptosis by Targeting Receptor-Interacting Serine/Threonine-Protein Kinase 3

(2019) Xinghui Li et al.   IMMUNITY

Necroptosis mediators RIPK3 and MLKL suppress intracellular Listeria replication independently of host cell killing

(2019) Kazuhito Sai et al.   JOURNAL OF CELL BIOLOGY

Structural and Functional Insights into Host Death Domains Inactivation by the Bacterial Arginine GlcNAcyltransferase Effector

(2019) Jingjin Ding et al.   MOLECULAR CELL

Flotillin-mediated endocytosis and ALIX–syntenin-1–mediated exocytosis protect the cell membrane from damage caused by necroptosis

(2019) Weiliang Fan et al.   Science Signaling

Potent and selective inhibitors of receptor-interacting protein kinase 1 that lack an aromatic back pocket group

(2019) Gregory L. Hamilton et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The Pyroptotic Cell Death Effector Gasdermin D Is Activated by Gout-Associated Uric Acid Crystals but Is Dispensable for Cell Death and IL-1β Release

(2019) Maryam Rashidi et al.   JOURNAL OF IMMUNOLOGY

Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis

(2019) Kim Newton et al.   NATURE

Viral MLKL Homologs Subvert Necroptotic Cell Death by Sequestering Cellular RIPK3

(2019) Emma J. Petrie et al.   Cell Reports

Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis

(2019) Melanie Fritsch et al.   NATURE

Activity of caspase-8 determines plasticity between cell death pathways

(2019) Kim Newton et al.   NATURE

Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity–independent pyroptosis, apoptosis, necroptosis, and inflammatory disease

(2019) R.K. Subbarao Malireddi et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease

(2019) Najoua Lalaoui et al.   NATURE

A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1

(2019) Panfeng Tao et al.   NATURE

The brace helices of MLKL mediate interdomain communication and oligomerisation to regulate cell death by necroptosis

(2018) Katherine A. Davies et al.   CELL DEATH AND DIFFERENTIATION

CRISPR whole-genome screening identifies new necroptosis regulators and RIPK1 alternative splicing

(2018) Marinella G. Callow et al.   Cell Death & Disease

Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis

(2018) Emma J. Petrie et al.   Nature Communications

TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and in Aging

(2018) Daichao Xu et al.   CELL

Mixed Lineage Kinase Domain-like Protein MLKL Breaks Down Myelin following Nerve Injury

(2018) Zhengxin Ying et al.   MOLECULAR CELL

RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation

(2018) Gianmaria Liccardi et al.   MOLECULAR CELL

MLKL, the Protein that Mediates Necroptosis, Also Regulates Endosomal Trafficking and Extracellular Vesicle Generation

(2017) Seongmin Yoon et al.   IMMUNITY

Kinase Activities of RIPK1 and RIPK3 Can Direct IFN-β Synthesis Induced by Lipopolysaccharide

(2017) Danish Saleh et al.   JOURNAL OF IMMUNOLOGY

Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases

(2017) Philip A. Harris et al.   JOURNAL OF MEDICINAL CHEMISTRY

Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis

(2017) Jiefei Geng et al.   Nature Communications

Evolutionary divergence of the necroptosis effector MLKL

(2016) M C Tanzer et al.   CELL DEATH AND DIFFERENTIATION

RIPK1 inhibits ZBP1-driven necroptosis during development

(2016) Kim Newton et al.   NATURE

Identification of a novel cell death-inducing domain reveals that fungal amyloid-controlled programmed cell death is related to necroptosis

(2016) Asen Daskalov et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

An evolutionary perspective on the necroptotic pathway

(2016) Yves Dondelinger et al.   TRENDS IN CELL BIOLOGY

TRAF2 is a biologically important necroptosis suppressor

(2015) S L Petersen et al.   CELL DEATH AND DIFFERENTIATION

Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis

(2015) D A Rodriguez et al.   CELL DEATH AND DIFFERENTIATION

NF-κB-Independent Role of IKKα/IKKβ in Preventing RIPK1 Kinase-Dependent Apoptotic and Necroptotic Cell Death during TNF Signaling

(2015) Yves Dondelinger et al.   MOLECULAR CELL

The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis

(2015) Michio Onizawa et al.   NATURE IMMUNOLOGY

The diverse role of RIP kinases in necroptosis and inflammation

(2015) John Silke et al.   NATURE IMMUNOLOGY

RIPK1 Regulates RIPK3-MLKL-Driven Systemic Inflammation and Emergency Hematopoiesis

(2014) James A. Rickard et al.   CELL

RIPK1- and RIPK3-induced cell death mode is determined by target availability

(2014) W D Cook et al.   CELL DEATH AND DIFFERENTIATION

RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity

(2014) Pratyusha Mandal et al.   MOLECULAR CELL

Mixed Lineage Kinase Domain-like Protein MLKL Causes Necrotic Membrane Disruption upon Phosphorylation by RIP3

(2014) Huayi Wang et al.   MOLECULAR CELL

Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death

(2014) Joanne M. Hildebrand et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition

(2013) Y Dondelinger et al.   CELL DEATH AND DIFFERENTIATION

Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death

(2013) Xin Chen et al.   CELL RESEARCH

Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis

(2013) Jianfeng Wu et al.   CELL RESEARCH

The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism

(2013) James M. Murphy et al.   IMMUNITY

Diverse Sequence Determinants Control Human and Mouse Receptor Interacting Protein 3 (RIP3) and Mixed Lineage Kinase domain-Like (MLKL) Interaction in Necroptotic Signaling

(2013) Wanze Chen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Toll-like Receptor 3-mediated Necrosis via TRIF, RIP3, and MLKL

(2013) William J. Kaiser et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

TNF can activate RIPK3 and cause programmed necrosis in the absence of RIPK1

(2013) D M Moujalled et al.   Cell Death & Disease

Structural Insights into RIP3-Mediated Necroptotic Signaling

(2013) Tian Xie et al.   Cell Reports

Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase

(2012) Liming Sun et al.   CELL

The RIP1/RIP3 Necrosome Forms a Functional Amyloid Signaling Complex Required for Programmed Necrosis

(2012) Jixi Li et al.   CELL

Necrostatin-1 blocks both RIPK1 and IDO: consequences for the study of cell death in experimental disease models

(2012) P Vandenabeele et al.   CELL DEATH AND DIFFERENTIATION

Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis

(2012) J. Zhao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models

(2012) N Takahashi et al.   Cell Death & Disease

Survival Function of the FADD-CASPASE-8-cFLIPL Complex

(2012) Christopher P. Dillon et al.   Cell Reports

RIP3 mediates the embryonic lethality of caspase-8-deficient mice

(2011) William J. Kaiser et al.   NATURE

Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis

(2011) Andrew Oberst et al.   NATURE

Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway

(2011) S. He et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phosphorylation-Driven Assembly of the RIP1-RIP3 Complex Regulates Programmed Necrosis and Virus-Induced Inflammation

(2009) YoungSik Cho et al.   CELL

Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α

(2009) Sudan He et al.   CELL

RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis

(2009) D.-W. Zhang et al.   SCIENCE

Identification of RIP1 kinase as a specific cellular target of necrostatins

(2008) Alexei Degterev et al.   Nature Chemical Biology