ArticleNature2011
COP1 is a tumour suppressor that causes degradation of ETS transcription factors.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 169 citations in OpenAlex.
- ETV1 Couples Reciprocal FGF23 and PTH Signaling to RenalResearch square · 2026Article
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- Uncovering the role of ETS2 in prostate cancer pathogenesis: relationship with p53 and ERG.Molecular biology reports · 2026Article
- Deubiquitination of ETV4 by USP7 Promotes NSCLC Tumorigenesis via MAPK7 Activation.Human mutation · 2026Article
- Emerging role of ETV4 in colorectal cancer: from molecular mechanisms to clinical implications.Frontiers in oncology · 2026Review
- ETV1 is a key regulator of enteroendocrine PYY production.Disease models & mechanisms · 2025Article
- Pseudokinase STK40 limits T cell exhaustion through COP1-dependent degradation of AP1-family transcription factors.Nature immunology · 2025Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- Enhanced ETS1 stability by DNAPKcs orchestrates transcriptional changes during chemoresistance in triple negative breast cancer.NPJ breast cancer · 2025Article
- COP1 Deficiency in BRAFCells · 2025Article
- DET1 dynamics underlie cooperative ubiquitination by CRL4Science advances · 2025Article
- Impairment of DET1 causes neurological defects and lethality in mice and humans.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Distinct roles of Constitutive Photomorphogenesis Protein 1 homolog (COP1) in human hepatocyte models.Frontiers in molecular biosciences · 2025Article
- Cell signaling inFrontiers in cellular and infection microbiology · 2025Review
- Rapid increase of C/EBPα p42 induces growth arrest of acute myeloid leukemia (AML) cells by Cop1 deletion in Trib1-expressing AML.Leukemia · 2024Article
- Identification of a novel MEF2C::SS18L1 fusion in childhood acute B-lymphoblastic leukemia.Journal of cancer research and clinical oncology · 2024Article
- ETV4 is a mechanical transducer linking cell crowding dynamics to lineage specification.Nature cell biology · 2024Article
- ETV4 mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer.Science advances · 2023Article
- E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function.Journal of biomedical science · 2023Review
- Effect of COP1 in Promoting the Tumorigenesis of Gastric Cancer by Down-Regulation of CDH18 via PI3K/AKT Signal Pathway.Analytical cellular pathology (Amsterdam) · 2023Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proto-oncogenes ETV1, ETV4 and ETV5 encode transcription factors in the E26 transformation-specific (ETS) family, which includes the most frequently rearranged and overexpressed genes in prostate cancer. Despite being critical regulators of development, little is known about their post-translational regulation. Here we identify the ubiquitin ligase COP1 (also known as RFWD2) as a tumour suppressor that negatively regulates ETV1, ETV4 and ETV5. ETV1, which is mutated in prostate cancer more often, was degraded after being ubiquitinated by COP1. Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs and was 50-fold more stable than wild-type ETV1. Almost all patient translocations render ETV1 insensitive to COP1, implying that this confers a selective advantage to prostate epithelial cells. Indeed, COP1 deficiency in mouse prostate elevated ETV1 and produced increased cell proliferation, hyperplasia, and early prostate intraepithelial neoplasia. Combined loss of COP1 and PTEN enhanced the invasiveness of mouse prostate adenocarcinomas. Finally, rare human prostate cancer samples showed hemizygous loss of the COP1 gene, loss of COP1 protein, and elevated ETV1 protein while lacking a translocation event. These findings identify COP1 as a tumour suppressor whose downregulation promotes prostatic epithelial cell proliferation and tumorigenesis.
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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.