ArticleScience signaling2018
Kinase domain dimerization drives RIPK3-dependent necroptosis.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Integrated Necroptosis Within Programmed Cell Death in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- Bilirubin directly activates RIPK3 to induce non-classical necroptosis.Cell discovery · 2026Article
- Research progress on programmed cell death of cardiomyocytes in pressure-overload hypertrophic cardiomyopathy.Apoptosis : an international journal on programmed cell death · 2025Review
- Structure-based design of potent and selective inhibitors targeting RIPK3 for eliminating on-target toxicity in vitro.Nature communications · 2025Article
- Elucidating the dual roles of apoptosis and necroptosis in diabetic wound healing: implications for therapeutic intervention.Burns & trauma · 2025Review
- An inducible RIPK3-driven necroptotic system enhances cancer cell-based immunotherapy and ensures safety.The Journal of clinical investigation · 2024Article
- Article
- Emerging role of immunogenic cell death in cancer immunotherapy.Frontiers in immunology · 2024Review
- The Molecular Mechanisms of Neuroinflammation in Alzheimer's Disease, the Consequence of Neural Cell Death.International journal of molecular sciences · 2023Review
- The double-edged functions of necroptosis.Cell death & disease · 2023Review
- From (Tool)Bench to Bedside: The Potential of Necroptosis Inhibitors.Journal of medicinal chemistry · 2023Review
- Tumor necroptosis-mediated shedding of cell surface proteins promotes metastasis of breast cancer by suppressing anti-tumor immunity.Breast cancer research : BCR · 2023Article
- Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases.Frontiers in immunology · 2023Review
- RIP3 Contributes to Cardiac Hypertrophy by Influencing MLKL-Mediated Calcium Influx.Oxidative medicine and cellular longevity · 2022Article
- The regulation of necroptosis by post-translational modifications.Cell death and differentiation · 2021Review
- Atg1 kinase in fission yeast is activated by Atg11-mediated dimerization and cis-autophosphorylation.eLife · 2020Article
- Expression of Protein Kinases RIPK-1 and RIPK-3 in Mouse and Human Hair Follicle.Doklady. Biochemistry and biophysics · 2020Article
- The Killer Pseudokinase Mixed Lineage Kinase Domain-Like Protein (MLKL).Cold Spring Harbor perspectives in biology · 2020Review
- Compound Prunetin Induces Cell Death in Gastric Cancer Cell with Potent Anti-Proliferative Properties: In Vitro Assay, Molecular Docking, Dynamics, and ADMET Studies.Biomolecules · 2020Article
- Necrostatin‑1 protects mice from acute lung injury by suppressing necroptosis and reactive oxygen species.Molecular medicine reports · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Necroptosis, an inflammatory form of cell death, is initiated by the activation of receptor-interacting protein kinase 3 (RIPK3), which depends on its interaction with RIPK1. Although catalytically inactive, the RIPK3 mutant D161N still stimulates RIPK1-dependent apoptosis and embryonic lethality in RIPK3 D161N homozygous mice. Whereas the absence of RIPK1 rescues RIPK3 D161N homozygous mice, we report that the absence of RIPK1 leads to embryonic lethality in RIPK3 D161N heterozygous mice. This suggested that the kinase domain of RIPK3 had a noncatalytic function that was enhanced by a conformation induced by the D161N mutation. We found that the RIPK3 kinase domain homodimerized through a surface that is structurally similar to that of the RAF family members. Mutation of residues at the dimer interface impaired dimerization and necroptosis. Kinase domain dimerization stimulated the activation of RIPK3 through cis-autophosphorylation. This noncatalytic, allosteric activity was enhanced by certain kinase-deficient mutants of RIPK3, including D161N. Furthermore, apoptosis induced by certain RIPK3 inhibitors was also dependent on the kinase dimerization interface. Our studies reveal that the RIPK3 kinase domain exhibits catalytically independent function that is important for both RIPK3-dependent necroptosis and apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.