ArticleEMBO molecular medicine2014
Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 121 citations in OpenAlex.
- HECT-type ubiquitin ligases: Emerging principles in the era of full-length structures.The Journal of biological chemistry · 2026Review
- WEE1 stabilizes MYC to promote therapeutic resistance in esophageal adenocarcinoma.Cancer letters · 2026Article
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- Article
- Chromosome 3p deletion leads to extensive genomic alterations in diverse cancers and confers synthetic lethality in uveal melanoma.bioRxiv : the preprint server for biology · 2026Article
- PAR-Driven Condensation Maintains Stalled Replication Fork Stability.bioRxiv : the preprint server for biology · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- MIZ-1 controls transcriptional programs required for BCR signaling, actin dynamics, and naïve B cell survival.Frontiers in immunology · 2026Article
- Enrichment-Free, Targeted Covalent Drug Discovery in Live Cells.ACS chemical biology · 2025Article
- AlphaFold-Guided Discovery of an Overlapping MYC/Miz-1 Interface Enables Peptidomimetic Disruption of MYC/MAX.ChemMedChem · 2025Article
- HUWE1 stimulates mTORC1 activity by enhancing Rheb interaction with mTORC1 and supports de novo pyrimidine synthesis.Cell reports · 2025Article
- Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1.Nature communications · 2025Article
- MAL2 and rab17 selectively redistribute invadopodia proteins to laterally-induced protrusions in hepatocellular carcinoma cells.Molecular biology of the cell · 2025Article
- Beyond small molecules: advancing MYC-targeted cancer therapies through protein engineering.Transcription · 2025Review
- The HOX Gene Family's Role as Prognostic and Diagnostic Biomarkers in Hematological and Solid Tumors.Cancers · 2025Review
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Chromosome 8q24 amplification associated with human hepatocellular carcinoma predicts MYC/ZEB1/MIZ1 transcriptional regulation.Scientific reports · 2024Article
- The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.Cell death discovery · 2023Review
- A small-molecule inhibitor of TopBP1 exerts anti-MYC activity and synergy with PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 5 countries.
Funding
Abstract
Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARF-BP1, MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high-throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells.
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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.