ArticleCell death and differentiation2019
The bromodomain protein BRD4 positively regulates necroptosis via modulating MLKL expression.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Regulatory complexity and therapeutic targeting of the necroptosis network.Frontiers in immunology · 2026Review
- The BRD4-nucleosome interaction is enhanced modestly and non-selectively by histone acetylation.Nucleic acids research · 2025Article
- Mixed Lineage Kinase Domain-Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Mitochondrial quality control as a therapeutic target in cardiovascular disease: Mechanistic insights and future directions.Journal of translational internal medicine · 2025Article
- Noncanonical feedback loop between "RIP3-MLKL" and "4EBP1-eIF4E" promotes neuronal necroptosis.MedComm · 2025Article
- MSCs Suppress Macrophage Necroptosis and Foster Liver Regeneration by Modulating SP1/SK1 Axis in Treating Acute Severe Autoimmune Hepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrating bioinformatics and experimental validation to Investigate IRF1 as a novel biomarker for nucleus pulposus cells necroptosis in intervertebral disc degeneration.Scientific reports · 2024Article
- cGAS-ISG15-RAGE axis reprogram necroptotic microenvironment and promote lymphatic metastasis in head and neck cancer.Experimental hematology & oncology · 2024Article
- Regulation of programmed cell death by Brd4.Cell death & disease · 2022Review
- Non-classical ferroptosis inhibition by a small molecule targeting PHB2.Nature communications · 2022Article
- Deficiency of PPP6C protects TNF-induced necroptosis through activation of TAK1.Cell death & disease · 2022Article
- BRD4-IRF1 axis regulates chemoradiotherapy-induced PD-L1 expression and immune evasion in non-small cell lung cancer.Clinical and translational medicine · 2022Article
- Necrostatin-1 Prevents Ferroptosis in a RIPK1- and IDO-Independent Manner in Hepatocellular Carcinoma.Antioxidants (Basel, Switzerland) · 2021Article
- MLKL in cancer: more than a necroptosis regulator.Cell death and differentiation · 2021Review
- The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line.Scientific reports · 2021Article
- Enhanced RIPK3 kinase activity-dependent lytic cell death in M1 but not M2 macrophages.Molecular immunology · 2021Article
- Sinapic Acid Reduces Oxidative Stress and Pyroptosis via Inhibition of BRD4 in Alcoholic Liver Disease.Frontiers in pharmacology · 2021Article
- Mitochondrial quality control mechanisms as molecular targets in cardiac ischemiaActa pharmaceutica Sinica. B · 2020Review
- Current translational potential and underlying molecular mechanisms of necroptosis.Cell death & disease · 2019Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis is a programmed form of necrotic cell death, which is tightly regulated by the necroptotic signaling pathway containing receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like (MLKL) protein. In addition to the RIP1-RIP3-MLKL axis, other factors regulating necroptosis are still largely unknown. Here a cell-based small-molecule screening led to the finding that BET inhibitors protected cells from necroptosis in the TNFα/Smac-mimetic/Z-VAD-FMK (TSZ)-induced cell necroptosis model. Mechanistic studies revealed that BET inhibitors acted by downregulating MLKL expression. Further research demonstrated that BRD4, IRF1, P-TEFb, and RNA polymerase II formed a transcription complex to regulate the expression of MLKL, and BET inhibitors interfered with the transcription complex formation. In necroptosis-related disease model, the BET inhibitor JQ-1 showed promising therapeutic effects. Collectively, our studies establish, for the first time, BRD4 as a new epigenetic factor regulating necroptosis, and highlight the potential of BET inhibitors in the treatment of necroptosis-related diseases.
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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.