ArticleGenes & development2004
Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kinetics.
Article in Genes & development, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 169 citations in OpenAlex.
- ZBTB7A as a novel vulnerability in neuroendocrine prostate cancer.Frontiers in endocrinology · 2023Article
- MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway.Scientific reports · 2022Article
- The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis.Cells · 2022Review
- Post-Translational Regulation of ARF: Perspective in Cancer.Biomolecules · 2020Review
- The p14ARF tumor suppressor restrains androgen receptor activity and prevents apoptosis in prostate cancer cells.Cancer letters · 2020Article
- HIV-1 Tat protein promotes neuronal dysregulation by inhibiting E2F transcription factor 3 (E2F3).The Journal of biological chemistry · 2019Article
- Novel Treatment of Hypertension by Specifically Targeting E2F for Restoration of Endothelial Dihydrofolate Reductase and eNOS Function Under Oxidative Stress.Hypertension (Dallas, Tex. : 1979) · 2019Article
- p53-independent role of MYC mutant T58A in the proliferation and apoptosis of breast cancer cells.Oncology letters · 2019Article
- Regulatory Network of ARF in Cancer Development.Molecules and cells · 2018Review
- Cycling to Meet Fate: Connecting Pluripotency to the Cell Cycle.Frontiers in cell and developmental biology · 2018Review
- SKP2 Activation by Thyroid Hormone Receptor β2 Bypasses Rb-Dependent Proliferation in Rb-Deficient Cells.Cancer research · 2017Article
- MDM2 but not MDM4 promotes retinoblastoma cell proliferation through p53-independent regulation of MYCN translation.Oncogene · 2017Article
- Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities.Cell discovery · 2017Article
- Dynamics of ARF regulation that control senescence and cancer.BMB reports · 2016Review
- Genetic perspective of retinoblastoma: From present to future.Indian journal of ophthalmology · 2016Review
- MDM2/MDMX: Master negative regulators for p53 and RB.Molecular & cellular oncology · 2016Article
- E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution.Cell death and differentiation · 2015Article
- p53-dependent gene repression through p21 is mediated by recruitment of E2F4 repression complexes.Oncogene · 2014Article
- E2F2 and CREB cooperatively regulate transcriptional activity of cell cycle genes.Nucleic acids research · 2013Article
- Loss of dE2F compromises mitochondrial function.Developmental cell · 2013Article
22 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
Abstract
Tumor development is dependent upon the inactivation of two key tumor-suppressor networks, p16(Ink4a)-cycD/cdk4-pRB-E2F and p19(Arf)-mdm2-p53, that regulate cellular proliferation and the tumor surveillance response. These networks are known to intersect with one another, but the mechanisms are poorly understood. Here, we show that E2F directly participates in the transcriptional control of Arf in both normal and transformed cells. This occurs in a manner that is significantly different from the regulation of classic E2F-responsive targets. In wild-type mouse embryonic fibroblasts (MEFs), the Arf promoter is occupied by E2F3 and not other E2F family members. In quiescent cells, this role is largely fulfilled by E2F3b, an E2F3 isoform whose function was previously undetermined. E2f3 loss is sufficient to derepress Arf, triggering activation of p53 and expression of p21(Cip1). Thus, E2F3 is a key repressor of the p19(Arf)-p53 pathway in normal cells. Consistent with this notion, Arf mutation suppresses the activation of p53 and p21(Cip1) in E2f3-deficient MEFs. Arf loss also rescues the known cell cycle re-entry defect of E2f3(-/-) cells, and this correlates with restoration of appropriate activation of classic E2F-responsive genes. Our data also demonstrate a direct role for E2F in the oncogenic activation of Arf. Specifically, we observe recruitment of the endogenous activating E2Fs, E2F1, and E2F3a, to the Arf promoter. Thus, distinct E2F complexes directly contribute to the normal repression and oncogenic activation of Arf. We propose that monitoring of E2F levels and/or activity is a key component of Arf's ability to respond to inappropriate, but not normal cellular proliferation.
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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.