ArticleScience translational medicine2015
Mortality factor 4 like 1 protein mediates epithelial cell death in a mouse model of pneumonia.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- MORF4L1 regulation and its role in chromatin remodeling, DNA damage, cellular senescence, and cardiometabolic disease.Vascular pharmacology · 2026Review
- The E3 ubiquitin ligase FBXL18 stabilizes BST2 to promote inflammation in RABV-infected astrocytes.Nature communications · 2025Article
- Structural and functional insights into the epigenetic regulator MRG15.Acta pharmacologica Sinica · 2024Review
- FBXL18 is required for ovarian cancer cell proliferation and migration through activating AKT signaling.American journal of translational research · 2024Article
- Protein arginine N-methyltransferase 4 (PRMT4) contributes to lymphopenia in experimental sepsis.Thorax · 2023Article
- Targeting MRG15 for the treatment of nonalcoholic steatohepatitis.Metabolism open · 2022Article
- Endotoxin stabilizes protein arginine methyltransferase 4 (PRMT4) protein triggering death of lung epithelia.Cell death & disease · 2021Article
- Review
- Necrostatin‑1 protects mice from acute lung injury by suppressing necroptosis and reactive oxygen species.Molecular medicine reports · 2020Article
- MRG15 orchestrates rhythmic epigenomic remodelling and controls hepatic lipid metabolism.Nature metabolism · 2020Article
- The RNFT2/IL-3Rα axis regulates IL-3 signaling and innate immunity.JCI insight · 2020Article
- Histone Deacetylase 11 Knockdown Blocks Larval Development and Metamorphosis in the Red Flour Beetle,Frontiers in genetics · 2020Article
- Network Pharmacology Integrated Molecular Docking Reveals the Mechanism of Anisodamine Hydrobromide Injection against Novel Coronavirus Pneumonia.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- MORF4L1 suppresses cell proliferation, migration and invasion by increasing p21 and E-cadherin expression in nasopharyngeal carcinoma.Oncology letters · 2019Article
- Lipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via an SCFJournal of cell science · 2017Article
- Receptor for advanced glycation end products is targeted by FBXO10 for ubiquitination and degradation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Oxidative stress destabilizes protein arginine methyltransferase 4 via glycogen synthase kinase 3β to impede lung epithelial cell migration.American journal of physiology. Cell physiology · 2017Article
- Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis.Science translational medicine · 2017Article
- Future Directions and Molecular Basis of Ventilator Associated Pneumonia.Canadian respiratory journal · 2017Review
- Antiinflammatory effects of bromodomain and extraterminal domain inhibition in cystic fibrosis lung inflammation.JCI insight · 2016Article
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11 authors at 2 institutions in 1 country.
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Abstract
Unchecked epithelial cell death is fundamental to the pathogenesis of pneumonia. The recognition of unique signaling pathways that preserve epithelial cell viability may present new opportunities for interventional strategies. We describe that mortality factor 4 like 1 (Morf4l1), a protein involved in chromatin remodeling, is constitutively expressed at low levels in the lung because of its continuous degradation mediated by an orphan ubiquitin E3 ligase subunit, Fbxl18. Expression of Morf4l1 increases in humans with pneumonia and is up-regulated in lung epithelia after exposure to Pseudomonas aeruginosa or lipopolysaccharide. In a mouse model of pneumonia induced by P. aeruginosa, Morf4l1 is stabilized by acetylation that protects it from Fbxl18-mediated degradation. After P. aeruginosa infection of mice, overexpression of Morf4l1 resulted in lung epithelial cell death, whereas its depletion restored cell viability. Using in silico modeling and drug-target interaction studies, we identified that the U.S. Food and Drug Administration-approved thrombin inhibitor argatroban is a Morf4l1 antagonist. Argatroban inhibited Morf4l1-dependent histone acetylation, reduced its cytotoxicity, and improved survival of mice with experimental lung injury at doses that had no anticoagulant activity. These studies uncover a previously unrecognized biological mechanism whereby pathogens subvert cell viability by extending the life span of a cytotoxic host protein. Morf4l1 may be a potential molecular target for non-antibiotic pharmacotherapy during severe pulmonary infection.
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