ArticleCell cycle (Georgetown, Tex.)2015
Regulating the stability and localization of CDK inhibitor p27(Kip1) via CSN6-COP1 axis.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Role of ubiquitin‑proteasome system in preeclampsia (Review).Molecular medicine reports · 2026Review
- TRIM21 functions as an oncogene in glioblastoma by transactivating FOSL1 and promoting the ubiquitination of p27.Cell communication and signaling : CCS · 2025Article
- STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57Journal of translational medicine · 2024Article
- Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Multiplexed cellular profiling identifies an organoselenium compound as an inhibitor of CRM1-mediated nuclear export.Traffic (Copenhagen, Denmark) · 2022Article
- Construction and validation of a prognostic risk model for breast cancer based on protein expression.BMC medical genomics · 2022Article
- RFWD2 induces cellular proliferation and selective proteasome inhibitor resistance by mediating P27 ubiquitination in multiple myeloma.Leukemia · 2021Article
- The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression.International journal of molecular sciences · 2021Review
- CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9.Cell death & disease · 2021Article
- Illuminating the COP1/SPA Ubiquitin Ligase: Fresh Insights Into Its Structure and Functions During Plant Photomorphogenesis.Frontiers in plant science · 2021Review
- Targeting RFWD2 as an Effective Strategy to Inhibit Cellular Proliferation and Overcome Drug Resistance to Proteasome Inhibitor in Multiple Myeloma.Frontiers in cell and developmental biology · 2021Article
- EGF Relays Signals to COP1 and Facilitates FOXO4 Degradation to Promote Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- CSN6: a promising target for cancer prevention and therapy.Histology and histopathology · 2020Review
- CSN6 promotes the cell migration of breast cancer cells by positively regulating Snail1 stability.International journal of medical sciences · 2020Observational
- Correlation of constitutive photomorphogenic 1 (COP1) and p27 tumor suppressor protein expression in ovarian cancer.Genes & genomics · 2019Article
- CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16Cancer biology & medicine · 2019Article
- CSN6 expression is associated with pancreatic cancer progression and predicts poor prognosis.Cancer biology & therapy · 2019Article
- CSN6 Promotes the Migration and Invasion of Cervical Cancer Cells by Inhibiting Autophagic Degradation of Cathepsin L.International journal of biological sciences · 2019Article
- COP9 signalosome subunit CSN5, but not CSN6, is upregulated in lung adenocarcinoma and predicts poor prognosis.Journal of thoracic disease · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The COP9 signalosome subunit 6 (CSN6), which is involved in ubiquitin-mediated protein degradation, is overexpressed in many types of cancer. CSN6 is critical in causing p53 degradation and malignancy, but its target in cell cycle progression is not fully characterized. Constitutive photomorphogenic 1 (COP1) is an E3 ubiquitin ligase associating with COP9 signalosome to regulate important target proteins for cell growth. p27 is a critical G1 CDK inhibitor involved in cell cycle regulation, but its upstream regulators are not fully characterized. Here, we show that the CSN6-COP1 link is regulating p27(Kip1) stability, and that COP1 is a negative regulator of p27(Kip1). Ectopic expression of CSN6 can decrease the expression of p27(Kip1), while CSN6 knockdown leads to p27(Kip1) stabilization. Mechanistic studies show that CSN6 interacts with p27(Kip1) and facilitates ubiquitin-mediated degradation of p27(Kip1). CSN6-mediated p27 degradation depends on the nuclear export of p27(Kip1), which is regulated through COP1 nuclear exporting signal. COP1 overexpression leads to the cytoplasmic distribution of p27, thereby accelerating p27 degradation. Importantly, the negative impact of COP1 on p27 stability contributes to elevating expression of genes that are suppressed through p27 mediation. Kaplan-Meier analysis of tumor samples demonstrates that high COP1 expression was associated with poor overall survival. These data suggest that tumors with CSN6/COP1 deregulation may have growth advantage by regulating p27 degradation and subsequent impact on p27 targeted genes.
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