ArticleCell death & disease2018
Proteasome inhibition blocks necroptosis by attenuating death complex aggregation.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma.Cell death & disease · 2026Article
- Proteasomal inhibition compromises microvascular integrity via distinct effects on non-immune endothelial cells and immune cells.Frontiers in immunology · 2026Article
- Human cytomegalovirus-triggered necroptosis is suppressed by sequestration of MLKL in the nucleus of infected monocytes.Journal of virology · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Polymorphisms in Necroptosis Pathway Genes: Novel Prognostic Markers for Multiple Myeloma Treatment Outcomes.International journal of molecular sciences · 2025Article
- Immunoaffinity proteomics for kidney injury biomarkers in male beagle dogs.EXCLI journal · 2024Article
- Proteasomal inhibitors induce myeloma cell pyroptosis via the BAX/GSDME pathway.Acta pharmacologica Sinica · 2023Article
- Article
- Necroptosis in CNS diseases: Focus on astrocytes.Frontiers in aging neuroscience · 2022Review
- Review
- The role of necroptosis in disease and treatment.MedComm · 2021Review
- A toolbox for imaging RIPK1, RIPK3, and MLKL in mouse and human cells.Cell death and differentiation · 2021Article
- Marizomib sensitizes primary glioma cells to apoptosis induced by a latest-generation TRAIL receptor agonist.Cell death & disease · 2021Article
- The potential role of necroptosis in clinical diseases (Review).International journal of molecular medicine · 2021Review
- Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Current translational potential and underlying molecular mechanisms of necroptosis.Cell death & disease · 2019Review
- Genome-Wide RNAi Screen Identifies Regulators of Cardiomyocyte Necrosis.ACS pharmacology & translational science · 2019Article
- Elimination of Osteosarcoma by Necroptosis with Graphene Oxide-Associated Anti-HER2 Antibodies.International journal of molecular sciences · 2019Review
- Herpes simplex virus 1 ICP6 impedes TNF receptor 1-induced necrosome assembly during compartmentalization to detergent-resistant membrane vesicles.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Proteasome inhibitors have achieved clinical success because they trigger intrinsic and extrinsic cell death to eliminate susceptible human cancers. The ubiquitin-proteasome protein degradation system regulates signaling pathways by controlling levels of components such as cellular inhibitor of apoptosis (cIAP)1 and cIAP2 in TNF-mediated cell death. Here, we sought to evaluate the contribution of necroptosis to the cell death pattern induced by the specific proteasome inhibitor Carfilzomib (Cf). Proteasome inhibitor-sensitive multiple myeloma cell lines die in response to Cf by apoptosis in combination with serine protease-dependent death, without any contribution of RIPK3-dependent necroptosis. Proteasome inhibition leads to the induction of apoptotic markers such as activated caspase-3 rather than necroptotic markers such as phosphorylated-MLKL in all cell lines tested. In HT-29 cells, Cf attenuates the late RIPK1 interaction with TNFR1 during TNF-induced necroptosis without altering the sensitivity of cIAP antagonists. Cf treatment results in decreased translocation of death signaling components RIPK1, FADD, caspase-8, cFLIP, and RIPK3 to detergent insoluble fractions. Our results show that proteasome inhibition with Cf impairs necroptosis and favors apoptosis even in cells with intact necroptotic machinery. Following the induction of TNFR1-mediated necroptosis, proteasome activity stabilizes effective aggregation and activation of ripoptosome/necrosome complexes.
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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.