ArticleAutophagy2024
The autophagy protein RUBCNL/PACER represses RIPK1 kinase-dependent apoptosis and necroptosis.
Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Programmed cell death in human respiratory syncytial virus infection.Frontiers in cellular and infection microbiology · 2025Pooled it
- Post-Translational Modifications in Traumatic Brain Injury: Decoding the Proteomic Landscape and Molecular Mechanisms of Secondary Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Single-cell spatial landscape of aggrephagy activity stratifies hepatocellular carcinoma neutrophils and delivers a 5-gene diagnostic panel for patient stratification.Translational oncology · 2026Article
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- TMBIM6 enhances dopaminergic neuron survival by modulating the IRE1a pathway in Parkinson's disease.Cell death & disease · 2026Article
- Macrophage C3aR1 Mediates Sepsis-Induced Myocardial Injury by Triggering Neutrophil Necroptosis.Journal of cellular and molecular medicine · 2026Article
- Looking at the fraction with Annexin V⁺ and propidium iodide⁺: insights into cell death types from preclinical studies in solid and haematological cancers.Apoptosis : an international journal on programmed cell death · 2026Review
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- LncRCD: A Comprehensive Database for Pan-Cancer Characterization of lncRNAs Related to 12 Regulated Cell Death Types.Computational and structural biotechnology journal · 2026Article
- The Interaction Between Ferroptosis and Necroptosis in Acute and Chronic Kidney Diseases.Journal of inflammation research · 2026Review
- IFT88/Kindlin-2 Signaling Prevents Mechanical Overloading-Induced PANoptosis of Nucleus Pulposus Cells by Activating FOXP1 SUMOylation.International journal of biological sciences · 2026Article
- The Molecular Mechanism of a Complex1-induced Apoptosis in Cancer Cells of the Esophagus.Current molecular medicine · 2026Article
- Article
- Inflammatory and Oxidative Biological Profiles in Mental Disorders: Perspectives on Diagnostics and Personalized Therapy.International journal of molecular sciences · 2025Review
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH.Viruses · 2025Review
- TAB2 deficiency induces dilated cardiomyopathy by promoting mitochondrial calcium overload in human iPSC-derived cardiomyocytes.Molecular medicine (Cambridge, Mass.) · 2025Article
- Lactylation: a novel driver of drug resistance in the tumor microenvironment.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Targeting ferroptosis, pyroptosis and necroptosis for cancer immunotherapy in melanoma: mechanistic insights and clinical perspectives.Frontiers in immunology · 2025Review
- Structural insights into Beclin 1 interactions with it's regulators for autophagy modulation.Computational and structural biotechnology journal · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) are used in cell therapy; nonetheless, their application is limited by their poor survival after transplantation in a proinflammatory microenvironment. Macroautophagy/autophagy activation in MSCs constitutes a stress adaptation pathway, promoting cellular homeostasis. Our proteomics data indicate that RUBCNL/PACER (RUN and cysteine rich domain containing beclin 1 interacting protein like), a positive regulator of autophagy, is also involved in cell death. Hence, we screened MSC survival upon various cell death stimuli under loss or gain of function of RUBCNL. MSCs were protected from TNF (tumor necrosis factor)-induced regulated cell death when RUBCNL was expressed. TNF promotes inflammation by inducing RIPK1 kinase-dependent apoptosis or necroptosis. We determine that MSCs succumb to RIPK1 kinase-dependent apoptosis upon TNF sensing and necroptosis when caspases are inactivated. We show that RUBCNL is a negative regulator of both RIPK1-dependent apoptosis and necroptosis. Furthermore, RUBCNL mutants that lose the ability to regulate autophagy, retain their function in negatively regulating cell death. We also found that RUBCNL forms a complex with RIPK1, which disassembles in response to TNF. In line with this finding, RUBCNL expression limits assembly of RIPK1-TNFRSF1A/TNFR1 complex I, suggesting that complex formation between RUBCNL and RIPK1 represses TNF signaling. These results provide new insights into the crosstalk between the RIPK1-mediated cell death and autophagy machineries and suggest that RUBCNL, due to its functional duality in autophagy and apoptosis/necroptosis, could be targeted to improve the therapeutic efficacy of MSCs.
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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 Socratic graph.