ArticleCell cycle (Georgetown, Tex.)2012
Overexpression of cyclin E/CDK2 complexes overcomes FGF-induced cell cycle arrest in the presence of hypophosphorylated Rb proteins.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 28 citations in OpenAlex.
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- The Role of Cell Cycle Regulators in Cell Survival-Dual Functions of Cyclin-Dependent Kinase 20 and p21International journal of molecular sciences · 2020Review
- Chinese Propolis Inhibits the Proliferation of Human Gastric Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Long non-coding RNA LINC-01572:28 inhibits granulosa cell growth via a decrease in p27 (Kip1) degradation in patients with polycystic ovary syndrome.EBioMedicine · 2018Article
- Fibronectin Promotes the Malignancy of Glioma Stem-Like Cells Via Modulation of Cell Adhesion, Differentiation, Proliferation and Chemoresistance.Frontiers in molecular neuroscience · 2018Article
- Cyclin E and FGF8 are downstream cell growth regulators in distinct tumor suppressor effects of ANXA7 in hormone-resistant cancer cells of breast versus prostate origin.Trends in cancer research · 2018Article
- The oncogenetic role of stanniocalcin 1 in lung adenocarcinoma: a promising serum candidate biomarker for tracking lung adenocarcinoma progression.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Inhibition of Cdk2 kinase activity selectively targets the CD44⁺/CD24⁻/Low stem-like subpopulation and restores chemosensitivity of SUM149PT triple-negative breast cancer cells.International journal of oncology · 2014Article
- Discrepancy between the effects of morronside on apoptosis in human embryonic lung fibroblast cells and lung cancer A549 cells.Oncology letters · 2014Article
- Cyclin D1 overexpression perturbs DNA replication and induces replication-associated DNA double-strand breaks in acquired radioresistant cells.Cell cycle (Georgetown, Tex.) · 2013Article
- Cyclin E2 induces genomic instability by mechanisms distinct from cyclin E1.Cell cycle (Georgetown, Tex.) · 2013Article
- Cell cycle-related kinase in carcinogenesis.Oncology letters · 2012Article
- A new mode of cell cycle stimulation: cyclin E and CDK2-mediated cytoplasmic retention of repressive E2F complexes.Cell cycle (Georgetown, Tex.) · 2012Article
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2 authors at 1 institution in 1 country.
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Abstract
FGF signaling inhibits chondrocyte proliferation and requires the function of the p107 and p130 members of the Rb protein family to execute growth arrest. p107 dephosphorylation plays a critical role in the chondrocyte response to FGF, as overexpression of cyclin D1/CDK4 complexes (the major p107 kinase) in rat chondrosarcoma (RCS) cells overcomes FGF-induced p107 dephosphorylation and growth arrest. In cells overexpressing cyclin D1/CDK4, FGF-induced downregulation of cyclin E/CDK2 activity was absent. To examine the role of cyclin E/CDK2 complexes in mediating FGF-induced growth arrest, this kinase was overexpressed in RCS cells. FGF-induced dephosphorylation of either p107 or p130 was not prevented by overexpressing cyclin E/CDK2 complexes. Unexpectedly, however, FGF-treated cells exhibited sustained proliferation even in the presence of hypophosphorylated p107 and p130. Both pocket proteins were able to form repressive complexes with E2F4 and E2F5 but these repressors were not translocated into the nucleus and therefore were unable to occupy their respective target DNA sites. Overexpressed cyclin E/CDK2 molecules were stably associated with p107 and p130 in FGF-treated cells in the context of E2F repressive complexes. Taken together, our data suggest a novel mechanism by which cyclin E/CDK2 complexes can promote cell cycle progression in the presence of dephosphorylated Rb proteins and provide a novel insight into the key Retinoblastoma/E2F/cyclin E pathway. Our data also highlight the importance of E2F4/p130 complexes for FGF-mediated growth arrest in chondrocytes.
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