ArticleProceedings of the National Academy of Sciences of the United States of America2012
Using targeted transgenic reporter mice to study promoter-specific p53 transcriptional activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- An Updated View of the Roles of p53 in Embryonic Stem Cells.Stem cells (Dayton, Ohio) · 2022Pooled it
- Mouse models to investigate in situ cell fate decisions induced by p53.The EMBO journal · 2024Article
- Revolutionizing Senescence Detection: Advancements from Traditional Methods to Cutting-Edge Techniques.Aging and disease · 2024Review
- Optimisation of TP53 reporters by systematic dissection of synthetic TP53 response elements.Nucleic acids research · 2023Article
- Cell Death and the p53 Enigma During Mammalian Embryonic Development.Stem cells (Dayton, Ohio) · 2022Review
- Precise tumor immune rewiring via synthetic CRISPRa circuits gated by concurrent gain/loss of transcription factors.Nature communications · 2022Article
- A noninvasive iRFP713 p53 reporter reveals dynamic p53 activity in response to irradiation and liver regeneration in vivo.Science signaling · 2022Article
- Developmental Acquisition ofGenes · 2021Review
- G1-phase progression in pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021Review
- Critical Role for P53 in Regulating the Cell Cycle of Ground State Embryonic Stem Cells.Stem cell reports · 2020Article
- p53 balances between tissue hierarchy and anarchy.Journal of molecular cell biology · 2019Review
- An Apela RNA-Containing Negative Feedback Loop Regulates p53-Mediated Apoptosis in Embryonic Stem Cells.Cell stem cell · 2015Article
- p53 suppresses tetraploid development in mice.Scientific reports · 2015Article
- New tricks for p53 regulation - restraint by protein coding RNAs.Cell & bioscience · 2015Article
- Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging.The Journal of clinical investigation · 2014Article
- Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism.Journal of inflammation (London, England) · 2014Review
- Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53.Nature communications · 2013Article
- How p53 wields the scales of fate: arrest or death?TranscriptionArticle
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53 transcription factor modulates gene expression programs that induce cell cycle arrest, senescence, or apoptosis, thereby preventing tumorigenesis. However, the mechanisms by which these fates are selected are unclear. Our objective is to understand p53 target gene selection and, thus, enable its optimal manipulation for cancer therapy. We have generated targeted transgenic reporter mice in which EGFP expression is driven by p53 transcriptional activity at a response element from either the p21 or Puma promoter, which induces cell cycle arrest/senescence and apoptosis, respectively. We demonstrate that we could monitor p53 activity in vitro and in vivo and detect variations in p53 activity depending on the response element, tissue type, and stimulus, thereby validating our reporter system and illustrating its utility for preclinical drug studies. Our results also show that the sequence of the p53 response element itself is sufficient to strongly influence p53 target gene selection. Finally, we use our reporter system to provide evidence for p53 transcriptional activity during early embryogenesis, showing that p53 is active as early as embryonic day 3.5 and that p53 activity becomes restricted to embryonic tissue by embryonic day 6.5. The data from this study demonstrate that these reporter mice could serve as powerful tools to answer questions related to basic biology of the p53 pathway, as well as cancer therapy and drug discovery.
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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.