Molecular Insights into the Mechanism of Necroptosis: The Necrosome as a Potential Therapeutic Target

The pseudokinase MLKL regulates hepatic insulin sensitivity independently of inflammation

(2019) Haixia Xu et al.   Molecular Metabolism

RIP1 kinase inhibitor halts the progression of an immune-induced demyelination disease at the stage of monocyte elevation

(2019) Sitao Zhang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis

(2019) Jooyeon Jhun et al.   Journal of Translational Medicine

Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation

(2019) Yves Dondelinger et al.   Nature Communications

RIPK1 inhibitor Cpd-71 attenuates renal dysfunction in cisplatin-treated mice via attenuating necroptosis, inflammation and oxidative stress

(2019) Jia-nan Wang et al.   CLINICAL SCIENCE

Necrostatin-1 attenuates renal ischemia/reperfusion injury by inhibiting necroptosis, oxidative stress, and inflammation via mediation of HIF-1α/miR-26a/TRPC6/PARP1 signaling

(2019) Bingbing Shen et al.   Molecular Therapy-Nucleic Acids

Necroptotic Cell Death Promotes Adaptive Immunity Against Colonizing Pneumococci

(2019) Ashleigh Nichole Riegler et al.   Frontiers in Immunology

RIP1/RIP3/MLKL mediates dopaminergic neuron necroptosis in a mouse model of Parkinson disease

(2019) Qing-Song Lin et al.   LABORATORY INVESTIGATION

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease

(2019) Maritza Oñate et al.   CELL DEATH AND DIFFERENTIATION

Enzymatic Self-Assembly Confers Exceptionally Strong Synergism with NF-κB Targeting for Selective Necroptosis of Cancer Cells

(2018) Jie Zhou et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

MLKL Requires the Inositol Phosphate Code to Execute Necroptosis

(2018) Cole M. Dovey et al.   MOLECULAR CELL

RGMb protects against acute kidney injury by inhibiting tubular cell necroptosis via an MLKL-dependent mechanism

(2018) Wenjing Liu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis

(2018) Huyan Meng et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Regulation of a distinct activated RIPK1 intermediate bridging complex I and complex II in TNFα-mediated apoptosis

(2018) Palak Amin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

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

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis

(2018) Johaiber Fuchslocher Chico et al.   Oncotarget

Pharmacological Inhibition of Necroptosis Protects from Dopaminergic Neuronal Cell Death in Parkinson’s Disease Models

(2018) Angelo Iannielli et al.   Cell Reports

Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: A mechanism involving calcium overload/XO/ROS/mPTP pathway

(2018) Pingjun Zhu et al.   Redox Biology

Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases

(2018) Hao Chi et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

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

(2017) Seongmin Yoon et al.   IMMUNITY

Thioredoxin-1 actively maintains the pseudokinase MLKL in a reduced state to suppress disulfide bond-dependent MLKL polymer formation and necroptosis

(2017) Eduardo Reynoso et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-Interacting Protein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome

(2017) Yan Ren et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

Necroptosis activation in Alzheimer's disease

(2017) Antonella Caccamo et al.   NATURE NEUROSCIENCE

PELI1 functions as a dual modulator of necroptosis and apoptosis by regulating ubiquitination of RIPK1 and mRNA levels of c-FLIP

(2017) Huibing Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

MLKL forms disulfide bond-dependent amyloid-like polymers to induce necroptosis

(2017) Shuzhen Liu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RIPK1 mediates a disease-associated microglial response in Alzheimer’s disease

(2017) Dimitry Ofengeim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis

(2017) Kelby W. Wegner et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

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

(2017) Jiefei Geng et al.   Nature Communications

Interferon-gamma regulates inflammatory cell death by targeting necroptosis in experimental autoimmune arthritis

(2017) Seung Hoon Lee et al.   Scientific Reports

RIPK3 Restricts Myeloid Leukemogenesis by Promoting Cell Death and Differentiation of Leukemia Initiating Cells

(2016) Ulrike Höckendorf et al.   CANCER CELL

K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo

(2016) B Shutinoski et al.   CELL DEATH AND DIFFERENTIATION

RIPK3 Activates Parallel Pathways of MLKL-Driven Necroptosis and FADD-Mediated Apoptosis to Protect against Influenza A Virus

(2016) Shoko Nogusa et al.   Cell Host & Microbe

Regulation of RIPK3- and RHIM-dependent Necroptosis by the Proteasome

(2016) Kenta Moriwaki et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Knockdown of RIPK1 Markedly Exacerbates Murine Immune-Mediated Liver Injury through Massive Apoptosis of Hepatocytes, Independent of Necroptosis and Inhibition of NF-κB

(2016) Jo Suda et al.   JOURNAL OF IMMUNOLOGY

The MLKL Channel in Necroptosis Is an Octamer Formed by Tetramers in a Dyadic Process

(2016) Deli Huang et al.   MOLECULAR AND CELLULAR BIOLOGY

Co-operative and Hierarchical Binding of c-FLIP and Caspase-8: A Unified Model Defines How c-FLIP Isoforms Differentially Control Cell Fate

(2016) Michelle A. Hughes et al.   MOLECULAR CELL

Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex

(2016) Tian-Min Fu et al.   MOLECULAR CELL

Sequential Engagement of Distinct MLKL Phosphatidylinositol-Binding Sites Executes Necroptosis

(2016) Giovanni Quarato et al.   MOLECULAR CELL

RIPK1 inhibits ZBP1-driven necroptosis during development

(2016) Kim Newton et al.   NATURE

RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation

(2016) Juan Lin et al.   NATURE

CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3

(2016) Jinho Seo et al.   NATURE CELL BIOLOGY

ATP-Competitive MLKL Binders Have No Functional Impact on Necroptosis

(2016) Bin Ma et al.   PLoS One

RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS

(2016) Yasushi Ito et al.   SCIENCE

Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis

(2016) X M Zhao et al.   Cell Death & Disease

HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death

(2016) A V Jacobsen et al.   Cell Death & Disease

The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance

(2016) Jérémie Gautheron et al.   Nature Communications

Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis

(2016) Shrikant R. Mulay et al.   Nature Communications

Critical function of the necroptosis adaptor RIPK3 in protecting from intestinal tumorigenesis

(2016) Dominique Bozec et al.   Oncotarget

Targeting macrophage necroptosis for therapeutic and diagnostic interventions in atherosclerosis

(2016) D. Karunakaran et al.   Science Advances

RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats

(2016) Yongjun Zhu et al.   PLoS One

Programmed Necrosis in the Cross Talk of Cell Death and Inflammation

(2015) Francis Ka-Ming Chan et al.   Annual Review of Immunology

Necroptosis signalling is tuned by phosphorylation of MLKL residues outside the pseudokinase domain activation loop

(2015) M. C. Tanzer et al.   BIOCHEMICAL JOURNAL

Necroptosis is preceded by nuclear translocation of the signaling proteins that induce it

(2015) S Yoon 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

Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics

(2015) Gi-Bang Koo et al.   CELL RESEARCH

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

Necroptosis and its role in inflammation

(2015) Manolis Pasparakis et al.   NATURE

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

Necroptosis: Pathway diversity and characteristics

(2015) M. Cristina de Almagro et al.   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

Absence of RIPK3 predicts necroptosis resistance in malignant melanoma

(2015) P Geserick et al.   Cell Death & Disease

A cellular screen identifies ponatinib and pazopanib as inhibitors of necroptosis

(2015) A Fauster et al.   Cell Death & Disease

Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death

(2015) K Moriwaki et al.   Cell Death & Disease

RIPK3 expression in cervical cancer cells is required for PolyIC-induced necroptosis, IL-1α release, and efficient paracrine dendritic cell activation

(2015) Susanne V. Schmidt et al.   Oncotarget

Activation of Necroptosis in Multiple Sclerosis

(2015) Dimitry Ofengeim et al.   Cell Reports

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

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

RIPK1 can function as an inhibitor rather than an initiator of RIPK3-dependent necroptosis

(2014) Conor J. Kearney et al.   FEBS Journal

Cutting Edge: RIPK1 Kinase Inactive Mice Are Viable and Protected from TNF-Induced Necroptosis In Vivo

(2014) Apostolos Polykratis et al.   JOURNAL OF IMMUNOLOGY

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

Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis

(2014) K. Newton et al.   SCIENCE

The B-RafV600E inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury

(2014) J-X Li et al.   Cell Death & Disease

MLKL Compromises Plasma Membrane Integrity by Binding to Phosphatidylinositol Phosphates

(2014) Yves Dondelinger et al.   Cell Reports

Positive and negative phosphorylation regulates RIP1- and RIP3-induced programmed necrosis

(2013) Thomas McQuade et al.   BIOCHEMICAL JOURNAL

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

(2013) Xin Chen et al.   CELL RESEARCH

The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism

(2013) James M. Murphy et al.   IMMUNITY

Combination of necroptosis and apoptosis inhibition enhances cardioprotection against myocardial ischemia–reperfusion injury

(2013) Shizuka Koshinuma et al.   Journal of Anesthesia

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

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

Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis

(2013) Zhenyu Cai et al.   NATURE CELL BIOLOGY

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

(2013) Juan Lin et al.   Cell Reports

Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia–reperfusion in vivo

(2012) Martinus I. F. J. Oerlemans et al.   BASIC RESEARCH IN CARDIOLOGY

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

(2012) Liming Sun et al.   CELL

Intermediate Domain of Receptor-interacting Protein Kinase 1 (RIPK1) Determines Switch between Necroptosis and RIPK1 Kinase-dependent Apoptosis

(2012) Linde Duprez et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

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

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

cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms

(2011) Maria Feoktistova et al.   MOLECULAR CELL

Virus Inhibition of RIP3-Dependent Necrosis

(2010) Jason W. Upton et al.   Cell Host & Microbe

Receptor-interacting protein (RIP) kinase family

(2010) Duanwu Zhang et al.   Cellular & Molecular Immunology

Enhanced Cytoprotective Effects of the Inhibitor of Apoptosis Protein Cellular IAP1 through Stabilization with TRAF2

(2009) Rebecca A. Csomos et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

TNF-α Induces Two Distinct Caspase-8 Activation Pathways

(2008) Lai Wang et al.   CELL