ArticleMolecular and cellular biology1998
The human ARF cell cycle regulatory gene promoter is a CpG island which can be silenced by DNA methylation and down-regulated by wild-type p53.
Article in Molecular and cellular biology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 353 citations in OpenAlex.
- Relationships between p14ARF Gene Methylation and Clinicopathological Features of Colorectal Cancer: A Meta-Analysis.PloS one · 2016Pooled it
- Identification of DMP1 as Novel p53 Repressed Transcriptional Target.International journal of molecular sciences · 2026Article
- Article
- ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors.Nature communications · 2023Article
- Gene Therapy with p14/tBID Induces Selective and Synergistic Apoptosis in Mutant Ras and Mutant p53 Cancer Cells In Vitro and In Vivo.Biomedicines · 2023Article
- Transcriptional regulation of INK4/ARF locus by cis and trans mechanisms.Frontiers in cell and developmental biology · 2022Review
- Mechanisms and Regulation of Cellular Senescence.International journal of molecular sciences · 2021Review
- Review
- AProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Aberrant DNA Methylation of Two Tumor Suppressor Genes,The international journal of occupational and environmental medicine · 2018Article
- p19Arf inhibits aggressive progression of H-ras-driven hepatocellular carcinoma.Carcinogenesis · 2018Article
- Epigenetics in Alzheimer's Disease: Perspective of DNA Methylation.Molecular neurobiology · 2018Review
- Long non-coding RNA ANRIL in gene regulation and its duality in atherosclerosis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2017Review
- Targeted DNA methylation in human cells using engineered dCas9-methyltransferases.Scientific reports · 2017Article
- Stabilization of the p53-DNA Complex by the Nuclear Protein Dmp1α.Cancer investigation · 2017Article
- Human papillomavirus oncogenic E6 protein regulates human β-defensin 3 (hBD3) expression via the tumor suppressor protein p53.Oncotarget · 2016Article
- Article
- The human ARF tumor suppressor senses blastema activity and suppresses epimorphic tissue regeneration.eLife · 2015Article
- Post-translational Down-regulation of Melanoma Antigen-A11 (MAGE-A11) by Human p14-ARF Tumor Suppressor.The Journal of biological chemistry · 2015Article
- Human DMTF1β antagonizes DMTF1α regulation of the p14(ARF) tumor suppressor and promotes cellular proliferation.Biochimica et biophysica acta · 2015Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The INK4a/ARF locus encodes two proteins involved in tumor suppression in a manner virtually unique in mammalian cells. Distinct first exons, driven from separate promoters, splice onto a common exon 2 and 3 but utilize different reading frames to produce two completely distinct proteins, both of which play roles in cell cycle control. INK4a, a critical element of the retinoblastoma gene pathway, binds to and inhibits the activities of CDK4 and CDK6, while ARF, a critical element of the p53 pathway, increases the level of functional p53 via interaction with MDM2. Here we clone and characterize the promoter of the human ARF gene and show that it is a CpG island characteristic of a housekeeping gene which contains numerous Sp1 sites. Both ARF and INK4a are coordinately expressed in cells except when their promoter regions become de novo methylated. In one of these situations, ARF transcription could be reactivated by treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine, and the reactivation kinetics of ARF and INK4a were found to differ slightly in a cell line in which both genes were silenced by methylation. The ARF promoter was also found to be highly responsive to E2F1 expression, in keeping with previous results at the RNA level. Lastly, transcription from the ARF promoter was down-regulated by wild-type p53 expression, and the magnitude of the effect correlated with the status of the endogenous p53 gene. This finding points to the existence of an autoregulatory feedback loop between p53, MDM2, and ARF, aimed at keeping p53 levels in check.
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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.