The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Cell fate decision mediated by p53 pulses
Open accessAbstract
The tumor suppressor p53 plays a crucial role in cellular response to various stresses. Recent experiments have shown that p53 level exhibits a series of pulses after DNA damage caused by ionizing radiation (IR). However, how the p53 pulses govern cell survival and death remains unclear. Here, we develop an integrated model with four modules for the p53 network and explore the mechanism for cell fate decision based on the dynamics of the network. By numerical simulations, the following processes are characterized. First, DNA repair proteins bind to IR-induced double-strand breaks, forming complexes, which are then detected by ataxia telangiectasia mutated (ATM). Activated ATM initiates the p53 oscillator to produce pulses. Consequently, the target genes of p53 are selectively induced to control cell fate. We propose that p53 promotes the repair of minor DNA damage but suppresses the repair of severe damage. We demonstrate that cell fate is determined by the number of p53 pulses relying on the extent of DNA damage. At low damage levels, few p53 pulses evoke cell cycle arrest by inducing p21 and promote cell survival, whereas at high damage levels, sustained p53 pulses trigger apoptosis by inducing p53AIP1. We find that p53 can effectively maintain genomic integrity by regulating the efficiency and fidelity of DNA repair. We also show that stochasticity in the generation and repair of DNA damage leads to variability in cell fate. These findings are consistent with experimental observations and advance our understanding of the dynamics and functions of the p53 network.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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 [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The BCL-2 protein family: opposing activities that mediate cell death
Youle, R. J., & Strasser, A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2308 · Cited by 4,806
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
The Bcl2 family: regulators of the cellular life-or-death switch
Cory, S., & Adams, J. M. (2002) · Nature Reviews Cancer · doi:10.1038/nrc883 · Cited by 4,032
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466
Live or let die: the cell's response to p53
Vousden, K. H., & Lü, X. (2002) · Nature reviews. Cancer · doi:10.1038/nrc864 · Cited by 3,231
Vousden, K. H., & Lane, D. P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2147 · Cited by 2,351
The Bcl-2 apoptotic switch in cancer development and therapy
Adams, J. M., & Cory, S. (2007) · Oncogene · doi:10.1038/sj.onc.1210220 · Cited by 2,256
The p53 pathway: positive and negative feedback loops
Harris, S. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208615 · Cited by 1,967
Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses
Rothkamm, K., & Löbrich, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0830918100 · Cited by 1,645
Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Tamai, K., Tokino, T., Nakamura, Y., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)00073-8 · Cited by 1,162
Cited by
Sorted by citations
DNA damage and the balance between survival and death in cancer biology
Roos, W. P., Thomas, A. D., & Kaina, B. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.2 · Cited by 1,189
Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia
Wong, T. N., Ramsingh, G., Young, A. L., Miller, C. A., Touma, W., Welch, J. S., Lamprecht, T. L., Shen, D., Hundal, J., Fulton, R. S., et al. (2015) · Nature · doi:10.1038/nature13968 · Cited by 892
Two-phase dynamics of p53 in the DNA damage response
Zhang, X.-P., Liu, F., & Wang, W. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100600108 · Cited by 333
“There has been much theoretical work on the mechanism of p53 oscillation (7, 8, 14).”
BackgroundInfluentialSelf-citationMirzayans, R., Andrais, B., Scott, A., & Murray, D. (2012) · Journal of Biomedicine and Biotechnology · doi:10.1155/2012/170325 · Cited by 257
“[67, 68] constructed an integrative computational model of the p53 network for ionizing radiation which was composed of four modules: DNA repair, ATM sensor, p53-centered feedback control, and cell fate decision.”
BackgroundDynamic modelling of oestrogen signalling and cell fate in breast cancer cells
Tyson, J. J., Baumann, W. T., Chen, C., Verdugo, A., Tavassoly, I., Wang, Y., Weiner, L. M., & Clarke, R. C. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3081 · Cited by 190
Metadata
- Authors
- Zhang, X.-P., Liu, F., Cheng, Z., & Wang, W.
- Affiliations
- National Laboratory of Solid State Microstructures (CN)
- University of California San Diego (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-07-28
- Volume
- 106
- Issue
- 30
- Pages
- 12245-12250
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2710988
- OpenAlex
- W2068371312
- Cited by
- 253
- References
- 59
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 12 · 2023: 9 · 2022: 16 · 2021: 19 · 2020: 20 · 2019: 17 · 2018: 7 · 2017: 12 · 2016: 15 · 2015: 16 · 2014: 19 · 2013: 13 · 2012: 23
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (10834002)
- Program for New Century Excellent Talents in University (NCET-08, NCET-08-0269)
- National Key Research and Development Program of China (2006CB910302, 2007CB814806)
- 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, p53 oscillations, cell fate determination, ionizing radiation, DNA damage response, ATM, DNA repair, DNA double-strand breaks, p21, p53AIP1, apoptosis, cell cycle arrest, genome stability, randomness
- MeSH terms
- Algorithms, Cell Survival, DNA Repair, DNA-Binding Proteins, Humans, Models, Biological, Protein Binding, Radiation, Ionizing, Signal Transduction, Tumor Suppressor Protein p53, Apoptosis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Proto-Oncogene Proteins c-bcl-2, Tumor Suppressor Proteins, Cytochromes c, Proto-Oncogene Proteins c-mdm2, Caspase 3, DNA Breaks, Double-Stranded, Ataxia Telangiectasia Mutated Proteins
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 ›
Are you an author, or do you see a problem with this page? Request a review
