ArticleCell death & disease2014
RIP3 is downregulated in human myeloid leukemia cells and modulates apoptosis and caspase-mediated p65/RelA cleavage.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 138 citations in OpenAlex.
- Programmed cell death in cancer: targeting necroptosis to kill tumor cell.Cell death discovery · 2026Review
- Mechanism and role of regulated cell death in tumor immunity and immunotherapy.Cancer communications (London, England) · 2025Review
- Spliceosome inhibition induces Z-RNA and ZBP1-driven cell death in small cell lung cancer.Cell reports · 2025Article
- The multiplex crosstalk between non-coding RNAs, programmed cell death and related mechanisms: a dynamic duo in hematological malignancies.Cancer cell international · 2025Review
- Polymorphisms in Necroptosis Pathway Genes: Novel Prognostic Markers for Multiple Myeloma Treatment Outcomes.International journal of molecular sciences · 2025Article
- Potential value and cardiovascular risks of programmed cell death in cancer treatment.Frontiers in pharmacology · 2025Review
- Construction and validation of a necroptosis-related lncRNA signature for predicting the prognosis of gastrointestinal cancer patients.Frontiers in immunology · 2025Article
- Development and validation of hierarchical signature for precision individualized therapy based on the landscape associated with necroptosis in clear cell renal cell carcinoma.Frontiers in pharmacology · 2025Article
- Identification of PANoptosis-based signature for predicting the prognosis and immunotherapy response in AML.Heliyon · 2024Article
- Prognostic significance and response to immune checkpoint inhibitors of RIPK3, MLKL and necroptosis in non-small cell lung cancer.Scientific reports · 2024Article
- Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity.Nature reviews. Cancer · 2024Review
- Deregulation of New Cell Death Mechanisms in Leukemia.Cancers · 2024Review
- Determinants for Antitumor and Protumor Effects of Programmed Cell Death.Cancer immunology research · 2024Article
- Identification of a novel necroptosis-related LncRNA signature for prognostic prediction and immune response in oral squamous cell carcinoma.Cancer biomarkers : section A of Disease markers · 2024Article
- Dual roles of inflammatory programmed cell death in cancer: insights into pyroptosis and necroptosis.Frontiers in pharmacology · 2024Review
- Identification and validation of a novel necroptosis-related molecular signature to evaluate prognosis and immune features in breast cancer.Apoptosis : an international journal on programmed cell death · 2023Article
- Necroptosis-related genes are associated with prognostic features of kidney renal clear cell carcinoma.Discover oncology · 2023Article
- Exploration and validation of a novel signature of seven necroptosis-related genes to improve the clinical outcome of hepatocellular carcinoma.BMC cancer · 2023Article
- The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Review
- Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma.European journal of medical research · 2023Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor-interacting protein kinase 3 (RIP3) associates with RIP1 in a necrosome complex that can induce necroptosis, apoptosis, or cell proliferation. We analyzed the expression of RIP1 and RIP3 in CD34+ leukemia cells from a cohort of patients with acute myeloid leukemia (AML) and CD34+ cells from healthy donors. RIP3 expression was significantly reduced in most AML samples, whereas the expression of RIP1 did not differ significantly. When re-expressed in the mouse DA1-3b leukemia cell line, RIP3 induced apoptosis and necroptosis in the presence of caspase inhibitors. Transfection of RIP3 in the WEHI-3b leukemia cell line or in the mouse embryonic fibroblasts also resulted in increased cell death. Surprisingly, re-expression of a RIP3 mutant with an inactive kinase domain (RIP3-kinase dead (RIP3-KD)) induced significantly more and earlier apoptosis than wild-type RIP3 (RIP3-WT), indicating that the RIP3 kinase domain is an essential regulator of apoptosis/necroptosis in leukemia cells. The induced in vivo expression of RIP3-KD but not RIP3-WT prolonged the survival of mice injected with leukemia cells. The expression of RIP3-KD induced p65/RelA nuclear factor-κB (NF-κB) subunit caspase-dependent cleavage, and a non-cleavable p65/RelA D361E mutant rescued these cells from apoptosis. p65/RelA cleavage appears to be at least partially mediated by caspase-6. These data indicate that RIP3 silencing in leukemia cells results in suppression of the complex regulation of the apoptosis/necroptosis switch and NF-κB activity.
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