ArticleNeoplasia (New York, N.Y.)2013
COP1 and GSK3β cooperate to promote c-Jun degradation and inhibit breast cancer cell tumorigenesis.
Article in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- Aldolase A accelerates hepatocarcinogenesis by refactoring c-Jun transcription.Journal of pharmaceutical analysis · 2025Article
- Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination.Science advances · 2024Article
- Identification of small molecules that suppress cell invasion and metastasis promoted by WASF3 activation.Heliyon · 2023Article
- Propagated Circulating Tumor Cells Uncover the Potential Role of NFκB, EMT, and TGFβ Signaling Pathways andCancers · 2023Article
- Endocrine resistance and breast cancer plasticity are controlled by CoREST.Nature structural & molecular biology · 2022Article
- Editorial: Emerging 3D and Animal Models in Diseases and Therapeutics.Frontiers in molecular biosciences · 2021Article
- Review
- miR-632 Promotes Laryngeal Carcinoma Cell Proliferation, Migration, and Invasion Through Negative Regulation of GSK3β.Oncology research · 2020Article
- Enhanced histone H3 acetylation of the PD-L1 promoter via the COP1/c-Jun/HDAC3 axis is required for PD-L1 expression in drug-resistant cancer cells.Journal of experimental & clinical cancer research : CR · 2020Article
- Timeless-Stimulated miR-5188-FOXO1/β-Catenin-c-Jun Feedback Loop Promotes Stemness via Ubiquitination of β-Catenin in Breast Cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Correlation of constitutive photomorphogenic 1 (COP1) and p27 tumor suppressor protein expression in ovarian cancer.Genes & genomics · 2019Article
- Article
- The PI3K/Akt/GSK-3β/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility.Cancer biology & medicine · 2019Article
- Aberrant GSK3β nuclear localization promotes AML growth and drug resistance.Blood advances · 2018Article
- miR-589 promotes gastric cancer aggressiveness by a LIFR-PI3K/AKT-c-Jun regulatory feedback loop.Journal of experimental & clinical cancer research : CR · 2018Article
- Ubiquitin-Specific Protease USP6 Regulates the Stability of the c-Jun Protein.Molecular and cellular biology · 2018Article
- Imaging and kinetics of the bimolecular complex formed by the tumor suppressor p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface plasmon resonance.International journal of nanomedicine · 2018Article
- Article
- miR-17-5p suppresses cell proliferation and invasion by targeting ETV1 in triple-negative breast cancer.BMC cancer · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
High abundance of c-Jun is detected in invasive breast cancer cells and aggressive breast tumor malignancies. Here, we demonstrate that a major cause of high c-Jun abundance in invasive breast cancer cells is prolonged c-Jun protein stability owing to poor poly-ubiquitination of c-Jun. Among the known c-Jun-targeting E3 ligases, we identified constitutive photomorphogenesis protein 1 (COP1) as an E3 ligase responsible for c-Jun degradation in less invasive breast cancer cells because depletion of COP1 reduced c-Jun poly-ubiquitination leading to the stabilization of c-Jun protein. In a panel of breast cancer cell lines, we observed an inverse association between the levels of COP1 and c-Jun. However, overexpressing COP1 alone was unable to decrease c-Jun level in invasive breast cancer cells, indicating that efficient c-Jun protein degradation necessitates an additional event. Indeed, we found that glycogen synthase kinase 3 (GSK3) inhibitors elevated c-Jun abundance in less invasive breast cancer cells and that GSK3β nonphosphorylable c-Jun-T239A mutant displayed greater protein stability and poorer poly-ubiquitination compared to the wild-type c-Jun. The ability of simultaneously enforced expression of COP1 and constitutively active GSK3β to decrease c-Jun abundance in invasive breast cancer cells allowed us to conclude that c-Jun is negatively regulated through the coordinated action of COP1 and GSK3β. Importantly, co-expressing COP1 and active GSK3β blocked in vitro cell growth/migration and in vivo metastasis of invasive breast cancer cells. Gene expression profiling of breast tumor specimens further revealed that higher COP1 expression correlated with better recurrence-free survival. Our study supports the notion that COP1 is a suppressor of breast cancer progression.
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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.