ArticleEMBO molecular medicine2017
HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation.
Article in EMBO molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 72 citations in OpenAlex.
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- Characterization of Korean Colorectal Cancer Reveals Novel Driver Gene and Clinically Relevant Mutations.MedComm · 2026Article
- Saga of MCL1 inhibitors in multiple myeloma.Biochemical pharmacology · 2026Review
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.bioRxiv : the preprint server for biology · 2025Article
- HUWE1 loss promotes stemness and drug resistance in CRC with dysregulated β-catenin destruction complex.Cell death discovery · 2025Article
- Cancer gene identification from RNA variant allelic frequencies using RVdriver.Genome biology · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Article
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- The E3 ligase HUWE1 increases the sensitivity of CRC to oxaliplatin through TOMM20 degradation.Oncogene · 2024Article
- Induced degradation of lineage-specific oncoproteins drives the therapeutic vulnerability of small cell lung cancer to PARP inhibitors.Science advances · 2024Article
- Effect of ubiquitin protease system on DNA damage response in prostate cancer (Review).Experimental and therapeutic medicine · 2024Review
- The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- E3 ubiquitin ligases in cancer stem cells: key regulators of cancer hallmarks and novel therapeutic opportunities.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways.Cell reports · 2023Article
- The Role of HECT E3 Ubiquitin Ligases in Colorectal Cancer.Biomedicines · 2023Review
- Expression Profile and Gene Regulation Network of NUSAP1 in Pan Cancers Based on Integrated Bioinformatics Analysis.International journal of general medicine · 2023Article
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis.Nature cell biology · 2022Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
Abstract
Cancer genome sequencing projects have identified hundreds of genetic alterations, often at low frequencies, raising questions as to their functional relevance. One exemplar gene is HUWE1, which has been found to be mutated in numerous studies. However, due to the large size of this gene and a lack of functional analysis of identified mutations, their significance to carcinogenesis is unclear. To determine the importance of HUWE1, we chose to examine its function in colorectal cancer, where it is mutated in up to 15 per cent of tumours. Modelling of identified mutations showed that they inactivate the E3 ubiquitin ligase activity of HUWE1. Genetic deletion of Huwe1 rapidly accelerated tumourigenic in mice carrying loss of the intestinal tumour suppressor gene Apc, with a dramatic increase in tumour initiation. Mechanistically, this phenotype was driven by increased MYC and rapid DNA damage accumulation leading to loss of the second copy of Apc The increased levels of DNA damage sensitised Huwe1-deficient tumours to DNA-damaging agents and to deletion of the anti-apoptotic protein MCL1. Taken together, these data identify HUWE1 as a bona fide tumour suppressor gene in the intestinal epithelium and suggest a potential vulnerability of HUWE1-mutated tumours to DNA-damaging agents and inhibitors of anti-apoptotic proteins.
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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.