ArticleCell death and differentiation2014
Distinct roles of RIP1-RIP3 hetero- and RIP3-RIP3 homo-interaction in mediating necroptosis.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers.
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Who cites it
183 citing papers in PubMed, 290 citations in OpenAlex.
- Article
- Disulfidptosis and its molecular mechanisms in cancer: mechanisms, regulation, and therapeutic potential.Medical oncology (Northwood, London, England) · 2026Review
- A non-classical necroptosis pathway mediated by caspases.Cell communication and signaling : CCS · 2026Article
- Targeting Ferroptosis and Necroptosis to Treat Stroke.Neurochemical research · 2026Review
- Bilirubin directly activates RIPK3 to induce non-classical necroptosis.Cell discovery · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Focus on necroptosis: its role in the pathogenesis and therapeutic potential of osteoarthritis.Frontiers in immunology · 2026Review
- Foot-and-mouth disease virus non-structural protein 3D induces necroptosis through interaction with RIPK3 in PK-15 and BHK-21 cells.Frontiers in veterinary science · 2026Article
- Decoding necrosome assembly: harmonizing signal amplification and attenuation through optimal RIP3 stoichiometry.Nature communications · 2025Article
- Induction of immunogenic necroptosis by shikonin in drug‑resistant head and neck squamous cell carcinoma cells.Oncology reports · 2025Article
- Resonance assignments of the human receptor interacting protein kinase 1 (RIPK1) in its fibrillar conformation.Biomolecular NMR assignments · 2025Article
- Trigger Points of Necroptosis (RIPK1, RIPK3, and MLKL)-Promising Horizon or Blind Alley in Therapy of Colorectal Cancer?International journal of molecular sciences · 2025Review
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Cell death in tumor microenvironment: an insight for exploiting novel therapeutic approaches.Cell death discovery · 2025Review
- Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice.Scientific reports · 2025Article
- Exploring TNFR1: from discovery to targeted therapy development.Journal of translational medicine · 2025Review
- Tumor Integrin-Targeted Glucose Oxidase Enzyme Promotes ROS-Mediated Cell Death that Combines with Interferon Alpha Therapy for Tumor Control.Molecular cancer therapeutics · 2025Article
- The interplay between α-synuclein aggregation and necroptosis in Parkinson's disease: a spatiotemporal perspective.Frontiers in neuroscience · 2025Review
- Elucidating the dual roles of apoptosis and necroptosis in diabetic wound healing: implications for therapeutic intervention.Burns & trauma · 2025Review
- Article
123 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis is mediated by a signaling complex called necrosome, containing receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like (MLKL). It is known that RIP1 and RIP3 form heterodimeric filamentous scaffold in necrosomes through their RIP homotypic interaction motif (RHIM) domain-mediated oligomerization, but the signaling events based on this scaffold has not been fully addressed. By using inducible dimer systems we found that RIP1-RIP1 interaction is dispensable for necroptosis; RIP1-RIP3 interaction is required for necroptosis signaling, but there is no necroptosis if no additional RIP3 protein is recruited to the RIP1-RIP3 heterodimer, and the interaction with RIP1 promotes the RIP3 to recruit other RIP3; RIP3-RIP3 interaction is required for necroptosis and RIP3-RIP3 dimerization is sufficient to induce necroptosis; and RIP3 dimer-induced necroptosis requires MLKL. We further show that RIP3 oligomer is not more potent than RIP3 dimer in triggering necroptosis, suggesting that RIP3 homo-interaction in the complex, rather than whether RIP3 has formed homo polymer, is important for necroptosis. RIP3 dimerization leads to RIP3 intramolecule autophosphorylation, which is required for the recruitment of MLKL. Interestingly, phosphorylation of one of RIP3 in the dimer is sufficient to induce necroptosis. As RIP1-RIP3 heterodimer itself cannot induce necroptosis, the RIP1-RIP3 heterodimeric amyloid fibril is unlikely to directly propagate necroptosis. We propose that the signaling events after the RIP1-RIP3 amyloid complex assembly are the recruitment of free RIP3 by the RIP3 in the amyloid scaffold followed by autophosphorylation of RIP3 and subsequent recruitment of MLKL by RIP3 to execute necroptosis.
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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.