ArticleNucleic acids research2006
Regulation of the human p21(waf1/cip1) gene promoter via multiple binding sites for p53 and the vitamin D3 receptor.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 247 citations in OpenAlex.
- Cooperation or Conflict? Molecular and Physiological Cross-Talk Between the Aryl Hydrocarbon and Vitamin D Receptors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Native Mass Spectrometry Reveals Binding Modes of the Tumor Suppressor Protein p53 to Different DNA Response Elements.Journal of the American Society for Mass Spectrometry · 2026Article
- Extracellular vesicles from long COVID patients promote RUNX2-mediated cellular stress via dysregulated miR-204 and p53 pathway activation.Cell communication and signaling : CCS · 2025Article
- Immunomodulatory role of vitamin D and emerging immunotherapies in hepatocellular carcinoma.Frontiers in nutrition · 2025Review
- Crosstalk between BER and NHEJ in XRCC4-Deficient Cells Depending on hTERT Overexpression.International journal of molecular sciences · 2024Article
- Vitamin D in Cancer Prevention and Treatment: A Review of Epidemiological, Preclinical, and Cellular Studies.Cancers · 2024Review
- Downregulation of Histone H3.3 Induces p53-Dependent Cellular Senescence in Human Diploid Fibroblasts.Genes · 2024Article
- The Influence of Single Nucleotide Polymorphisms on Vitamin D Receptor Protein Levels and Function in Chronic Liver Disease.International journal of molecular sciences · 2023Article
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- Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism.Frontiers in pharmacology · 2022Review
- Vitamin D: A Potential Star for Treating Chronic Pancreatitis.Frontiers in pharmacology · 2022Review
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- Epigenetics Involvement in Oxaliplatin-Induced Potassium Channel Transcriptional Downregulation and Hypersensitivity.Molecular neurobiology · 2021Article
- Comparing the Expressions of Vitamin D Receptor, Cell Proliferation, and Apoptosis in Gastric Mucosa With Gastritis, Intestinal Metaplasia, or Adenocarcinoma Change.Frontiers in medicine · 2021Article
- Policing Cancer: Vitamin D Arrests the Cell Cycle.International journal of molecular sciences · 2020Review
- Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications.Molecules (Basel, Switzerland) · 2020Review
- Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells.Nutrients · 2020Review
- Ezh2-dependent H3K27me3 modification dynamically regulates vitamin D3-dependent epigenetic control of CYP24A1 gene expression in osteoblastic cells.Journal of cellular physiology · 2020Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The main regulator of the human tumor suppresser gene p21(waf1/cip1) is the transcription factor p53, but more recently it has been suggested to be a primary anti-proliferative target for the nuclear receptor VDR in the presence of its ligand 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). To identify VDR responding regions, we analyzed 20 overlapping regions covering the first 7.1 kb of the p21(waf1/cip1) promoter in MCF-7 human breast cancer cells using chromatin immuno-precipitation assays (ChIP) with antibodies against p53 and VDR. We confirmed two known p53 binding regions at approximate positions -1400 and -2300 and identified a novel site at position -4500. In addition, we found three VDR-associated promoter regions at positions -2300, -4500 and -6900, i.e. two regions showed binding for both p53 and VDR. In silico screening and in vitro binding assays using recombinant and in vitro translated proteins identified five p53 binding sites within the three p53-positive promoter regions and also five 1alpha,25(OH)2D3 response elements within the three VDR-positive regions. Reporter gene assays confirmed the expected responsiveness of the respective promoter regions to the p53 inducer 5-fluorouracil and 1alpha,25(OH)2D3. Moreover, re-ChIP assays confirmed the functionality of the three 1alpha,25(OH)2D3-reponsive promoter regions by monitoring simultaneous occupancy of VDR with the co-activator proteins CBP, SRC-1 and TRAP220. Taken together, we demonstrated that the human p21((waf1/cip1)) gene is a primary 1alpha,25(OH)2D3-responding gene with at least three VDR binding promoter regions, in two of which also p53 co-localizes.
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