p53 Dynamics Control Cell Fate
Open accessAbstract
Dynamic Responses: Expression of the tumor suppressor p53 is activated in response to cell stress. The dynamics of p53 activation can vary, depending on the stressor, resulting in either pulsatile or constant p53 levels; however, the functional consequence of these different dynamics is unclear. Purvis et al. (p. 1440 ) developed a method to control p53 dynamics in human cells. Pulsing p53 selectively activated genes involved in cell cycle arrest and DNA repair, allowing recovery from DNA damage. In contrast, sustained p53 promoted induction of terminal genes leading to cellular senescence. Thus, protein dynamics can affect cell fate decisions.
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Target genes were reported to be activated by p53 with varying kinetics through stimulus- and promoter-specific recruitment of transcription initiation components and polymerase II.
“Target genes were reported to be activated by p53 with varying kinetics through stimulus- and promoter-specific recruitment of transcription initiation components and polymerase II.60, 61, 62, 63”
From Census and evaluation of p53 target genes (2017) · cites this paper as [63]
PML and YPEL3 are among GATA4-induced genes.
“previously identified regulators of senescence, such as promyelocytic leukemia protein (PML) and yippee-like 3 (YPEL3), are among GATA4-induced genes (fig. S6D) (53).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [53]
TP53 plays a central role in regulating cellular responses to genotoxic stress.
“TP53 plays a central role in regulating cellular responses to genotoxic stress13–17”
From Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia (2015) · cites this paper as [15]
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- Authors
- Purvis, J. E., Karhohs, K. W., Mock, C., Batchelor, E., Loewer, A., & Lahav, G.
- Affiliations
- Harvard University (US)
- Corresponding author
- Lahav, Galit
- Venue
- Science
- Published
- 2012-06-15
- Volume
- 336
- Issue
- 6087
- Pages
- 1440-1444
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4162876
- OpenAlex
- W2066218351
- Cited by
- 770
- References
- 75
- Citations by year
- 2026: 42 · 2025: 38 · 2024: 44 · 2023: 50 · 2022: 64 · 2021: 70 · 2020: 50 · 2019: 55 · 2018: 65 · 2017: 60 · 2016: 64 · 2015: 53 · 2014: 59 · 2013: 43 · 2012: 12
- FWCI
- 26.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R00GM102372, R01GM083303, GM083303, F32GM095168, K99GM102372)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- p53, cell fate, DNA damage response, DNA double-strand breaks, computational modeling, cellular senescence, downstream gene expression
- MeSH terms
- Promyelocytic Leukemia Protein, DNA Repair, Gamma Rays, Humans, Imidazoles, Models, Biological, Nuclear Proteins, Piperazines, Transcription Factors, Signal Transduction, Transcriptional Activation, Tumor Suppressor Protein p53, Cellular Senescence, Apoptosis, Tumor Suppressor Proteins, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, DNA Breaks, Double-Stranded, Single-Cell Analysis, Cell Cycle Checkpoints
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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