ArticleCell2013
The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability.
Article in Cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers.
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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.
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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
213 citing papers in PubMed, 370 citations in OpenAlex.
- Endogenous protein tagging coupled with a CRISPR screening approach identifies UBE3C as a potential MYC oncogene regulator.Scientific reports · 2026Article
- Loss of FBXO11 establishes a stem cell program in acute myeloid leukemia by dysregulating LONP1.The Journal of clinical investigation · 2026Article
- Cedrol impedes lung cancer metastasis by reducing tumor-associated macrophage polarization mediated by MYC-driven aerobic glycolysis.Human cell · 2025Article
- The ESCRT protein CHMP5 promotes T cell leukemia by enabling BRD4-p300-dependent transcription.Nature communications · 2025Article
- Increased expression of FBW7 may improve the prognosis of lung adenocarcinoma after pemetrexed chemotherapy by transforming the epithelial-to-mesenchymal process.Journal of thoracic disease · 2025Article
- The rewired immune microenvironment in leukemia.Nature immunology · 2025Review
- Decoding the functional impact of the cancer genome through protein-protein interactions.Nature reviews. Cancer · 2025Review
- FBXW7/GSK3β-mediated proline-rich 11 degradation promotes oxidative DNA damage and inhibits tumor progression in renal cell carcinoma.Theranostics · 2025Article
- Uncovering cell-type-specific immunomodulatory variants and molecular phenotypes in COVID-19 using structurally resolved protein networks.Cell reports · 2024Article
- The KLF16/MYC feedback loop is a therapeutic target in bladder cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- NMolecular medicine (Cambridge, Mass.) · 2024Review
- Biologic and Clinical Analysis of Childhood Gamma Delta T-ALL Identifies LMO2/STAG2 Rearrangements as Extremely High Risk.Cancer discovery · 2024Article
- Article
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- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Epidermal growth factor receptor (EGFR) is a target of the tumor-suppressor E3 ligase FBXW7.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.Frontiers in pharmacology · 2024Review
- Idasanutlin and navitoclax induce synergistic apoptotic cell death in T-cell acute lymphoblastic leukemia.Leukemia · 2023Article
- ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.Nature communications · 2023Article
153 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
Sequencing efforts led to the identification of somatic mutations that could affect the self-renewal and differentiation of cancer-initiating cells. One such recurrent mutation targets the binding pocket of the ubiquitin ligase Fbxw7. Missense FBXW7 mutations are prevalent in various tumors, including T cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. Here, we show that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity. Finally, we demonstrated that small-molecule-mediated suppression of MYC activity leads to T-ALL remission, suggesting an effective therapeutic strategy.
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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.