ArticleThe Journal of clinical investigation2011
Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 128 citations in OpenAlex.
- Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026Review
- RFWD2 Mitigates AD-Like Cognitive Impairments via the JNK-SGK1 Signaling Pathway in Mice.CNS neuroscience & therapeutics · 2026Article
- CRISPR knockout screens reveal JUN as the master mediator of resistance to MAPK inhibition in KRAS-mutant pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Cryo-EM structure of the human COP1-DET1 ubiquitin ligase complex.Nature communications · 2026Article
- Deubiquitination of ETV4 by USP7 Promotes NSCLC Tumorigenesis via MAPK7 Activation.Human mutation · 2026Article
- The Genomic Basis of the Svalbard Reindeer's Adaptation to an Extreme Arctic Environment.Genome biology and evolution · 2025Article
- Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines.ACS bio & med chem Au · 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
- A Perspective on Therapeutic Targeting Against Ubiquitin Ligases to Stabilize Tumor Suppressor Proteins.Cancers · 2025Review
- Distinct roles of Constitutive Photomorphogenesis Protein 1 homolog (COP1) in human hepatocyte models.Frontiers in molecular biosciences · 2025Article
- Rapid increase of C/EBPα p42 induces growth arrest of acute myeloid leukemia (AML) cells by Cop1 deletion in Trib1-expressing AML.Leukemia · 2024Article
- Single-cell image-based genetic screens systematically identify regulators of Ebola virus subcellular infection dynamics.bioRxiv : the preprint server for biology · 2024Article
- Constitutive photomorphogenic protein 1 ubiquitinates interleukin-1 receptor accessory protein in human liver cancer.Journal of cancer research and clinical oncology · 2023Article
- Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy.Genes & diseases · 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
- Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases.Frontiers in immunology · 2023Review
- Article
- A COP1-GATA2 axis suppresses AR signaling and prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- COP1 Acts as a Ubiquitin Ligase for PCDH9 Ubiquitination and Degradation in Human Glioma.Molecular neurobiology · 2022Article
- [Effects of ring finger and tryptophan-aspartic acid 2 on dendritic spines and synapse formation in cerebral cortex neurons of mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biochemical studies have suggested conflicting roles for the E3 ubiquitin ligase constitutive photomorphogenesis protein 1 (Cop1; also known as Rfwd2) in tumorigenesis, providing evidence for both the oncoprotein c-Jun and the tumor suppressor p53 as its targets. Here we present what we believe to be the first in vivo investigation of the role of Cop1 in cancer etiology. Using an innovative genetic approach to generate an allelic series of Cop1, we found that Cop1 hypomorphic mice spontaneously developed malignancy at a high frequency in the first year of life and were highly susceptible to radiation-induced lymphomagenesis. Further analysis revealed that c-Jun was a key physiological target for Cop1 and that Cop1 constitutively kept c-Jun at low levels in vivo and thereby modulated c-Jun/AP-1 transcriptional activity. Importantly, Cop1 deficiency stimulated cell proliferation in a c-Jun-dependent manner. Focal deletions of COP1 were observed at significant frequency across several cancer types, and COP1 loss was determined to be one of the mechanisms leading to c-Jun upregulation in human cancer. We therefore conclude that Cop1 is a tumor suppressor that functions, at least in part, by antagonizing c-Jun oncogenic activity. In the absence of evidence for a genetic interaction between Cop1 and p53, our data strongly argue against the use of Cop1-inhibitory drugs for cancer therapy.
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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.