ArticleEndocrinology2010
Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition.
Article in Endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 63 citations in OpenAlex.
- Cancer Reversion Therapy: Prospects, Progress and Future Directions.Current issues in molecular biology · 2025Review
- Recent Advances in Structural Optimization of Quinazoline-Based Protein Kinase Inhibitors for Cancer Therapy (2021-Present).Molecules (Basel, Switzerland) · 2024Review
- Synthesis, docking, MD simulation, ADMET, drug likeness, and DFT studies of novel furo[2,3-b]indol-3a-ol as promising Cyclin-dependent kinase 2 inhibitors.Scientific reports · 2024Article
- Exploring gene-patient association to identify personalized cancer driver genes by linear neighborhood propagation.BMC bioinformatics · 2024Article
- Medicinal chemistry perspective of pyrido[2,3-RSC advances · 2023Review
- Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors.Life (Basel, Switzerland) · 2022Review
- Identifying Novel Drug Targets by iDTPnd: A Case Study of Kinase Inhibitors.Genomics, proteomics & bioinformatics · 2021Article
- Heterogeneity of Colorectal Cancer Progression: Molecular Gas and Brakes.International journal of molecular sciences · 2021Review
- Policing Cancer: Vitamin D Arrests the Cell Cycle.International journal of molecular sciences · 2020Review
- Relevance of Vitamin D in Melanoma Development, Progression and Therapy.Anticancer research · 2020Review
- Cell Cycle Proteins as Key Regulators of Postmitotic Cell Death.The Yale journal of biology and medicine · 2019Review
- Association among plasma 1,25(OH)The Prostate · 2019Article
- Inhibition of cyclin-dependent kinase 2 protects against doxorubicin-induced cardiomyocyte apoptosis and cardiomyopathy.The Journal of biological chemistry · 2018Article
- Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management.Laboratory investigation; a journal of technical methods and pathology · 2017Review
- Cyclin-Dependent Kinase 2 Promotes Tumor Proliferation and Induces Radio Resistance in Glioblastoma.Translational oncology · 2016Article
- Commonalities in the Association between PPARG and Vitamin D Related with Obesity and Carcinogenesis.PPAR research · 2016Review
- Vitamin D and urological cancers.Central European journal of urology · 2016Review
- Insights on Structural Characteristics and Ligand Binding Mechanisms of CDK2.International journal of molecular sciences · 2015Review
- Osteopontin-c mediates the upregulation of androgen responsive genes in LNCaP cells through PI3K/Akt and androgen receptor signaling.Oncology letters · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), inhibits proliferation of a variety of cell types including adenocarcinoma of the prostate. We have previously shown that 1,25-(OH)(2)D(3) increases the stability of the cyclin-dependent kinase inhibitor p27(KIP1), decreases cyclin-dependent kinase 2 (CDK2) activity, and promotes G(1) phase accumulation in human prostate cancer cells. These effects correlate with cytoplasmic relocalization of CDK2. In this study, we investigated the role of CDK2 cytoplasmic relocalization in the antiproliferative effects of 1,25-(OH)(2)D(3). CDK2 was found to be necessary for prostate cancer cell proliferation. Although induced by 1,25-(OH)(2)D(3), the cyclin-dependent kinase inhibitor p27(KIP1) was dispensable for 1,25-(OH)(2)D(3)-mediated growth inhibition. Reduction in CDK2 activity by 1,25-(OH)(2)D(3) was associated with decreased T160 phosphorylation, a residue whose phosphorylation in the nucleus is essential for CDK2 activity. Ectopic expression of cyclin E was sufficient to overcome 1,25-(OH)(2)D(3)-mediated cytoplasmic mislocalization of CDK2 and all antiproliferative effects of 1,25-(OH)(2)D(3), yet endogenous levels of cyclin E or binding to CDK2 were not affected by 1,25-(OH)(2)D(3). Similarly, knockdown of the CDK2 substrate retinoblastoma, which causes cyclin E up-regulation, resulted in resistance to 1,25-(OH)(2)D(3)-mediated growth inhibition. Human prostate cancer cells resistant to growth inhibition by 1,25-(OH)(2)D(3) but retaining fully functional vitamin D receptors were developed. These cells did not exhibit 1,25-(OH)(2)D(3)-mediated cytoplasmic relocalization of CDK2. Targeting CDK2 to the nucleus of 1,25-(OH)(2)D(3)-sensitive cancer cells blocked G(1) accumulation and growth inhibition by 1,25-(OH)(2)D(3). These data establish central roles for CDK2 nuclear-cytoplasmic trafficking and cyclin E in the mechanism of 1,25-(OH)(2)D(3)-mediated growth inhibition in prostate cancer cells.
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