ArticleCell death and differentiation2020
Beclin 1 functions as a negative modulator of MLKL oligomerisation by integrating into the necrosome complex.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Emerging role of copper in the pathophysiology of spinal cord injury.Neural regeneration research · 2026Article
- Toxicarioside H induces cytoprotective autophagy by hindering the progression of necroptosis in triple-negative breast cancer cells.Translational oncology · 2026Article
- USP13 depletion sensitizes colorectal cancer cells to necroptosis by destabilizing cIAP2 proteins.Cell death and differentiation · 2026Article
- The Biological Role and Clinical Significance of BECLIN-1 in Cancer.International journal of molecular sciences · 2025Review
- Loss of Beclin 1 primes colorectal cancer cells for Immunogenic necroptosis via transcriptional de-repression of RIPK1/RIPK3/MLKL axis.Molecular biology reports · 2025Article
- Opposing regulation of the K63-linked polyubiquitination of RIPK3 by SMURF1 and USP5 in necroptosis.Nature communications · 2025Article
- Review
- The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH.Viruses · 2025Review
- CO confers neuroprotection via activating the PERK-calcineurin pathway and inhibiting necroptosis.Cell death discovery · 2025Article
- Different types of cell death and their interactions in myocardial ischemia-reperfusion injury.Cell death discovery · 2025Review
- Beclin 1 prevents ISG15-mediated cytokine storms to secure fetal hematopoiesis and survival.The Journal of clinical investigation · 2025Article
- MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis.Autophagy · 2025Article
- Necroptosis-based glioblastoma prognostic subtypes: implications for TME remodeling and therapy response.Annals of medicine · 2024Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- The autophagy protein RUBCNL/PACER represses RIPK1 kinase-dependent apoptosis and necroptosis.Autophagy · 2024Article
- Necroptosis-related lncRNA-based novel signature to predict the prognosis and immune landscape in soft tissue sarcomas.Journal of cancer research and clinical oncology · 2024Article
- Beclin-1: a therapeutic target at the intersection of autophagy, immunotherapy, and cancer treatment.Frontiers in immunology · 2024Review
- Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- IKK-mediated TRAF6 and RIPK1 interaction stifles cell death complex assembly leading to the suppression of TNF-α-induced cell death.Cell death and differentiation · 2023Article
- Myeloid autophagy genes protect mice against fatal TNF- and LPS-induced cytokine storm syndromes.Autophagy · 2023Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis is a form of regulated cell death caused by formation of the necrosome complex. However, the factors modulating this process and the systemic pathophysiological effects of necroptosis are yet to be understood. Here, we identified that Beclin 1 functions as an anti-necroptosis factor by being recruited into the necrosome complex upon treatment with TNFα, Smac mimetic, and pan-caspase inhibitor and by repressing MLKL oligomerisation, thus preventing the disruption of the plasma membrane. Cells ablated or knocked-out for Beclin 1 become sensitised to necroptosis in an autophagy-independent manner without affecting the necrosome formation itself. Interestingly, the recruitment of Beclin 1 into the necrosome complex is dependent on the activation and phosphorylation of MLKL. Biochemically, the coiled-coil domain (CCD) of Beclin 1 binds to the CCD of MLKL, which restrains the oligomerisation of phosphorylated MLKL. Finally, Beclin 1 depletion was found to promote necroptosis in leukaemia cells and enhance regression of xenografted-tumour upon treatment with Smac mimetics and caspase inhibitors. These results suggest that Beclin 1 functions as a negative regulator in the execution of necroptosis by suppressing MLKL oligomerisation.
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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.