ArticleThe Journal of clinical investigation2011
Subunit 6 of the COP9 signalosome promotes tumorigenesis in mice through stabilization of MDM2 and is upregulated in human cancers.
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 75 papers.
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Who cites it
75 citing papers in PubMed, 106 citations in OpenAlex.
- CSN6 Promotes Pancreatic Cancer Progression and Gemcitabine Resistance via Antagonizing DCAF1-Mediated Ubiquitination of NPM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mechanisms and potential applications of COPS6 in pan-cancer therapy.World journal of clinical oncology · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Review
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- Computational exploration of the significance ofWorld journal of clinical oncology · 2023Article
- Genomics of deletion 7 and 7q in myeloid neoplasm: from pathogenic culprits to potential synthetic lethal therapeutic targets.Leukemia · 2023Article
- COPS6 promotes tumor progression and reduces CD8Acta pharmacologica Sinica · 2023Article
- eIF3f Mediates SGOC Pathway Reprogramming by Enhancing Deubiquitinating Activity in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- FBXW7β loss-of-function enhances FASN-mediated lipogenesis and promotes colorectal cancer growth.Signal transduction and targeted therapy · 2023Article
- The COP9 signalosome complex regulates fungal development and virulence in the wheat scab fungusFrontiers in microbiology · 2023Article
- COP9 signalosome deletion promotes renal injury and distal convoluted tubule remodeling.American journal of physiology. Renal physiology · 2022Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Analysis of expression profiles and prognostic value of COP9 signalosome subunits for patients with head and neck squamous cell carcinoma.Oncology letters · 2021Article
- The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression.International journal of molecular sciences · 2021Review
- Impact of diabetes on promoting the growth of breast cancer.Cancer communications (London, England) · 2021Article
- Article
- CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9.Cell death & disease · 2021Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
The mammalian constitutive photomorphogenesis 9 (COP9) signalosome (CSN), a protein complex involved in embryonic development, is implicated in cell cycle regulation and the DNA damage response. Its role in tumor development, however, remains unclear. Here, we have shown that the COP9 subunit 6 (CSN6) gene is amplified in human breast cancer specimens, and the CSN6 protein is upregulated in human breast and thyroid tumors. CSN6 expression positively correlated with expression of murine double minute 2 (MDM2), a potent negative regulator of the p53 tumor suppressor. Expression of CSN6 appeared to prevent MDM2 autoubiquitination at lysine 364, resulting in stabilization of MDM2 and degradation of p53. Mice in which Csn6 was deleted died early in embryogenesis (E7.5). Embryos lacking both Csn6 and p53 survived to later in embryonic development (E10.5), which suggests that loss of p53 could partially rescue the effect of loss of Csn6. Mice heterozygous for Csn6 were sensitized to γ-irradiation-induced, p53-dependent apoptosis in both the thymus and the developing CNS. These mice were also less susceptible than wild-type mice to γ-irradiation-induced tumorigenesis. These results suggest that loss of CSN6 enhances p53-mediated tumor suppression in vivo and that CSN6 plays an important role in regulating DNA damage-associated apoptosis and tumorigenesis through control of the MDM2-p53 signaling pathway.
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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.