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.
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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 [16]
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Goldbeter, A. (2017) · Chaos An Interdisciplinary Journal of Nonlinear Science · doi:10.1063/1.4990783 · Cited by 51 · see citing works
Kocik, J., Machula, M., Wisniewska, A., Surmiak, E., Holak, T. A., & Skalniak, L. (2019) · Cancers · doi:10.3390/cancers11071014 · Cited by 46 · see citing works
“Since the transition from p53ARRESTER to p53KILLER requires the accumulation of HIPK2 kinase (homeodomain-interacting protein kinase 2) in response to severe DNA damage [25] and normally occurs after several cycles of the induction of p53ARRESTER protein [22,26,27], it is not easily achieved by a rough p53 release evo…”
BackgroundKuchina, A., Espinar, L., García‐Ojalvo, J., & Süel, G. M. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002273 · Cited by 49 · see citing works
“Similar bursts of promoter activity and protein localization in single cells have also been reported in other systems, and have been attributed to the stochastic and reversible nature of the underlying biochemical reactions [43,45,46,47,48,49,50].”
BackgroundNutlins and Ionizing Radiation in Cancer Therapy
Impicciatore, G. G., Sancilio, S., Miscia, S., & Pietro, R. D. (2010) · Current Pharmaceutical Design · doi:10.2174/138161210791033932 · Cited by 49 · see citing works
“[113] proposed an interesting model of the p53-signalling network sustaining a dual transcriptionindependent role for p53 in DNA repair that would be favoured in the presence of low DNA damage or prevented when damage is severe.”
Backgroundp53 dynamics orchestrates with binding affinity to target genes for cell fate decision
Wu, M., Ye, H., Tang, Z., Shao, C., Lu, G., Chen, B., Yang, Y., Wang, G., & Hao, H. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.492 · Cited by 49 · see citing works
“These results are in accordance with a previous theoretical prediction that the number of pulses might be an indicator of cell fate decision.(29) We then asked why the increased number of p53 pulses is closely associated with the appearance of terminal pulse and why differential features of p53 dynamics, pulsed and su…”
ResultOscillatory control of signalling molecules
Paszek, P., Jackson, D. A., & White, M. (2010) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.08.004 · Cited by 45 · see citing works
Cun, Y., Dai, N., Xiong, C., Li, M., Sui, J.-D., Qian, C., Li, Z., & Wang, D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055313 · Cited by 45 · see citing works
“p53 not only promotes the repair of minor DNA damage induced by radiation but also induces apoptosis of cells with severe DNA damage [43].”
BackgroundRetractedLi, Y., Li, Y., Zhang, H., & Chen, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026302 · Cited by 45 · see citing works
“The oscillation (pulses) could provide potential precise regulation, such as the digital response of p53 to DNA damage [28,29].”
BackgroundMoore, R., Ooi, H. K., Kang, T., Bleris, L. G., & Ma, L. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004653 · Cited by 45 · see citing works
“A previous modeling study has proposed the role of a different positive feedback loop in enhancing the robust stability of p53 oscillation [61], whereby the cytosolic MDM2 protein translocates into nucleus to interact with the mRNA of p53 through direct binding and promote the translation of p53 mRNA to close the loop…”
BackgroundModeling the Basal Dynamics of P53 System
Sun, T., Yang, W., Liu, J., & Shen, P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027882 · Cited by 42 · see citing works
Ye, Y., Kang, X., Bailey, J., Li, C., & Hong, T. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006855 · Cited by 42 · see citing works
DNA-PKCS binding to p53 on the p21WAF1/CIP1 promoter blocks transcription resulting in cell death
Hill, R., Madureira, P. A., Waisman, D. M., & Lee, P. W. K. (2011) · Oncotarget · doi:10.18632/oncotarget.378 · Cited by 43 · see citing works
“More recent data suggest that it is the control over p53-mediated p21 expression that ultimately determines cell fate, with ATM/ATR and DNA-PK promoting and suppressing p21 expression, resulting in cell cycle arrest and apoptosis, respectively [40-43].”
RetractedWong, G. C., & Chow, H. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220203 · Cited by 40 · see citing works
Liu, B., Bhatt, D., Oltvai, Z. N., Greenberger, J. S., & Bahar, İ. (2014) · Scientific Reports · doi:10.1038/srep06245 · Cited by 40 · see citing works
Kumar, R. J., Chao, H. X., Simpson, D. A., Feng, W., Cho, M.-G., Roberts, V., Sullivan, A. R., Shah, S., Wozny, A., Fagan‐Solis, K. D., et al. (2020) · NAR Cancer · doi:10.1093/narcan/zcaa038 · Cited by 39 · see citing works
Zhao, L., Sun, T., Pei, J., & Ouyang, Q. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1502126112 · Cited by 38 · see citing works
Smith, G. R., & Shanley, D. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011092 · Cited by 39 · see citing works
“There have been many other papers [70,71,134,135] modelling aspects of the behaviour of p53, though these have mostly concentrated on the negative feedback control through its transcription of the ubiquitin ligase MDM2 and resulting degradation, which can produce oscillations in protein concentration.”
BackgroundDecision making of the p53 network: Death by integration
Li, Z., Ni, M., Li, J., Zhang, Y., Ouyang, Q., & Tang, C. (2010) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2010.11.041 · Cited by 37 · see citing works
“Some recent studies focused on the role of post-translational modifications of p53 for its target-gene selectivity in cell fate decision (Olsson et al., 2007; Zhang et al., 2009).”
The relationship between DNA single-stranded damage response and double-stranded damage response
Ma, A., & Dai, X. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1403681 · Cited by 38 · see citing works
“P53 accumulation rate determines the threshold of apoptosis, the slower cumulative rate, the higher threshold of apoptosis and the less likely to apoptosis [16,34].”
BackgroundSharma, S. K., & Münger, K. (2020) · mBio · doi:10.1128/mbio.01190-20 · Cited by 34 · see citing works
Tian, X., Liu, F., Zhang, X. P., Li, J., & Wang, W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038164 · Cited by 32 · see citing works
“Most previous models assumed that cells always first arrest the cell cycle to fix DNA damage no matter how severe it is [20,21].”
BackgroundMethodInfluentialSelf-citationMulti-synchronization and other patterns of multi-rhythmicity in oscillatory biological systems
Goldbeter, A., & Yan, J. (2022) · Interface Focus · doi:10.1098/rsfs.2021.0089 · Cited by 34 · see citing works
Snoopy’s hybrid simulator: a tool to construct and simulate hybrid biological models
Herajy, M., Liu, F., Röhr, C., & Monika Heiner, A. (2017) · BMC Systems Biology · doi:10.1186/s12918-017-0449-6 · Cited by 31 · see citing works
Self-citationCoordination of the Nuclear and Cytoplasmic Activities of p53 in Response to DNA Damage
Tian, P., Zhang, X. P., Liu, F., & Wang, W. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.07.042 · Cited by 31 · see citing works
Self-citationThe role of mRNA decay in p53-induced gene expression
Melanson, B. D., Bose, R., Hamill, J. D., Marcellus, K. A., Pan, E., & McKay, B. C. (2011) · RNA · doi:10.1261/rna.030122.111 · Cited by 30 · see citing works
“following the activation of p53 by DNA double-strand breaks is proportional to the extent of DNA damage, and sustained p53–Mdm2 oscillations are thought to contribute to the decision to undergo apoptosis in response to p53 activation (Lahav 2004, 2008; Geva-Zatorsky et al. 2006; Proctor and Gray 2008; Batchelor et al.…”
BackgroundInfluentialInvolvement of miR-605 and miR-34a in the DNA Damage Response Promotes Apoptosis Induction
Zhou, C.-H., Zhang, X., Liu, F., & Wang, W. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.02.032 · Cited by 30 · see citing works
Self-citationShen, B., Zhao, K., Ma, S., Yuan, D., & Bai, Y. (2014) · Chemistry - An Asian Journal · doi:10.1002/asia.201403117 · Cited by 30 · see citing works
AtPDCD5 Plays a Role in Programmed Cell Death after UV-B Exposure in Arabidopsis
Ferreyra, M. L. F., Casadevall, R., D’Andrea, L., AbdElgawad, H., Beemster, G. T. S., & Casati, P. (2016) · PLANT PHYSIOLOGY · doi:10.1104/pp.16.00033 · Cited by 29 · see citing works
Hanson, R. L., Porter, J. R., & Batchelor, E. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201803063 · Cited by 29 · see citing works
Dynamics of P53 in response to DNA damage: Mathematical modeling and perspective
Sun, T., & Cui, J. (2015) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.08.017 · Cited by 28 · see citing works
Oscillatory dynamics of p38 activity with transcriptional and translational time delays
Zhang, Y., Liu, H., Yan, F., & Zhou, J. (2017) · Scientific Reports · doi:10.1038/s41598-017-11149-5 · Cited by 28 · see citing works
Coordination of the AMPK, Akt, mTOR, and p53 Pathways under Glucose Starvation
Zhou, Y., & Liu, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314945 · Cited by 30 · see citing works
“Based on its different phosphorylation status, p53p is further divided into p53-arrester and p53-killer, inducing cell-cycle arrest and apoptosis, respectively [38,39].”
BackgroundMethodSelf-citationDose-Response Modeling of Etoposide-Induced DNA Damage Response
Li, Z., Sun, B., Clewell, R. A., Adeleye, Y. A., Andersen, M. E., & Zhang, Q. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft259 · Cited by 28 · see citing works
“p53 and its regulated targets function cooperatively to make appropriate cell fate decisions depending on the severity of DNA damage (Zhang et al., 2009).”
BackgroundSchonn, I., Hennesen, J., & Dartsch, D. C. (2010) · APOPTOSIS · doi:10.1007/s10495-010-0564-y · Cited by 26 · see citing works
“It has recently been described that pulsatile p53 activation is one of the determinants of cellular fate [47], but since HT29cells express mutated p53 devoid of its normal tumour suppressing functions, this may not be a relevant mechanism in our setting.”
Regulation of the DNA Damage Response by p53 Cofactors
Zhang, X. P., Liu, F., & Wang, W. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2012.04.002 · Cited by 26 · see citing works
Self-citationATM and ATR Activation Through Crosstalk Between DNA Damage Response Pathways
Fedak, E. A., Adler, F. R., Abegglen, L. M., & Schiffman, J. D. (2021) · Bulletin of Mathematical Biology · doi:10.1007/s11538-021-00868-6 · Cited by 26 · see citing works
“ATM becomes active when it binds to the ends of a double-stranded DNA break (DSB) or when it encounters catalysts in the large mass around a DSB, called a focus (van den Bosch et al. 2003; Adamowicz 2018; Dupré et al. 2006; Lavin et al. 2015; Ma et al. 2005; Zhang et al. 2009).”
BackgroundDifferential p53-Mediated Cellular Responses to DNA-Damaging Therapeutic Agents
Carlsen, L., & El‐Deiry, W. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111828 · Cited by 24 · see citing works
“The persistence of damage [53], the status and activity of various DNA repair pathways [12,54], the kinetics of the p53 response [38–41], and cellular heterogeneity [12,15,41,52] also impact on the various observed effects on p53 and its function.”
BackgroundOrlandella, F. M., Smaldone, G., Salvatore, G., Vitagliano, L., Cianflone, A., Parasole, R., Beneduce, G., Menna, G., Salvatore, M., & Mirabelli, P. (2021) · Biomarker Research · doi:10.1186/s40364-021-00307-7 · Cited by 23 · see citing works
Guedj, A., Geiger-Maor, A., Benyamini, H., Nevo, Y., Elgavish, S., Galun, E., Amsalem, H., & Rachmilewitz, J. (2016) · Aging · doi:10.18632/aging.101120 · Cited by 22 · see citing works
“The specific dynamics of p53 were found to depend on the extent and persistence of damage and leads to the expression of a different set of downstream genes [36, 37], that in turn activates alternative cellular outcomes ranging from DNA repair, transient cell cycle arrest, or in the case of unresolved damage senescenc…”
BackgroundPDCD5 functions as a regulator of p53 dynamics in the DNA damage response
Zhuge, C., Sun, X., Chen, Y., & Lei, J. (2015) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2015.09.025 · Cited by 22 · see citing works
“Based on the integrated models in Zhang et al. (2009, 2011), it has shown that cell fate was governed by the number of p53 pulses during DNA ator of p53 dynamics in the DNA damage response.”
BackgroundMethodResultInfluentialPDCD5-Regulated Cell Fate Decision after Ultraviolet-Irradiation-Induced DNA Damage
Zhuge, C., Chang, Y., Li, Y., Chen, Y., & Lei, J. (2011) · Biophysical Journal · doi:10.1016/j.bpj.2011.10.044 · Cited by 22 · see citing works
Regulation of Tip60‐dependent p53 acetylation in cell fate decision
Wang, P., Bao, H., Zhang, X., Liu, F., & Wang, W. (2018) · FEBS Letters · doi:10.1002/1873-3468.13287 · Cited by 21 · see citing works
Self-citationIwamoto, K., Hamada, H., Eguchi, Y., & Okamoto, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101333 · Cited by 21 · see citing works
“Although the simulated results by conventional models showed a tendency of decline in SF with increasing IR-dose [14,38], there was no comparison of the simulated results with experimentally observed data.”
BackgroundResultInfluentialATM in focus: A damage sensor and cancer target
Khalil, H. S., Tummala, H., & Zhelev, N. (2012) · Biodiscovery · doi:10.7750/biodiscovery.2012.5.1 · Cited by 20 · see citing works
“DNA repair, cell cycle arrest or apoptosis [169-172].”
Dynamics of intracellular information decoding
Kobayashi, T. J., & Kamimura, A. (2011) · Physical Biology · doi:10.1088/1478-3975/8/5/055007 · Cited by 21 · see citing works
TP53 in Myelodysplastic Syndromes
Jiang, Y., Gao, S., Soubise, B., Douet‐Guilbert, N., Liu, Z., & Troadec, M. (2021) · Cancers · doi:10.3390/cancers13215392 · Cited by 21 · see citing works
“If there are high levels of DNA damage, sustained TP53 pulses suppress DNA repair and induce apoptosis [26,27].”
BackgroundFANCI functions as a repair/apoptosis switch in response to DNA crosslinks
Shah, R. B., Kernan, J. L., van Hoogstraten, A., Ando, K., Li, Y., Belcher, A. L., Mininger, I., Bussenault, A. M., Raman, R., Ramanagoudr‐Bhojappa, R., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.06.010 · Cited by 19 · see citing works
Hu, G., Xu, S., & Wang, J. (2015) · Chemical Biology & Drug Design · doi:10.1111/cbdd.12598 · Cited by 19 · see citing works
Roles of cellular heterogeneity, intrinsic and extrinsic noise in variability of p53 oscillation
Wang, D.-G., Wang, S., Huang, B. Y., & Liu, F. (2019) · Scientific Reports · doi:10.1038/s41598-019-41904-9 · Cited by 19 · see citing works
Self-citationCoordination of miR-192 and miR-22 in p53-Mediated Cell Fate Decision
Sun, C., Zhang, X., & Wang, W. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194768 · Cited by 19 · see citing works
“Selective expression of p53-targeted genes is crucial for the decision between survival and death in response to DNA damage [5,6].”
BackgroundSelf-citationMicroRNAs and the DNA damage response: How is cell fate determined?
Visser, H., & Thomas, A. D. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103245 · Cited by 19 · see citing works
Coordination between p21 and DDB2 in the Cellular Response to UV Radiation
Li, H., Zhang, X., & Liu, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080111 · Cited by 19 · see citing works
“depends on the severity of DNA damage [6,7].”
BackgroundSelf-citationUdden, S. M. N., Morita‐Fujimura, Y., Satake, M., & Ikawa, S. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.10.005 · Cited by 19 · see citing works
Kobayashi, H., Shigetomi, H., Nishio, M., Umetani, M., Imanaka, S., & Hashimoto, H. (2025) · Antioxidants · doi:10.3390/antiox15010003 · Cited by 18 · see citing works
“Moderate and sustained activation promotes senescence, whereas strong activation or severe DNA damage triggers apoptosis via PUMA, Phorbol-12-Myristate-13-Acetate-induced protein 1 (NOXA), Bcl-2-associated X protein (BAX), and other effectors [99,100].”
Non-Gaussian noise-weakened stability in a foraging colony system with time delay
Dong, X., Zeng, C., Yang, F., Guan, L., Xie, Q., & Duan, W.-L. (2017) · Physica A Statistical Mechanics and its Applications · doi:10.1016/j.physa.2017.11.015 · Cited by 18 · see citing works
Comprehensive Bioinformatic Investigation of TP53 Dysregulation in Diverse Cancer Landscapes
Khan, R., Puszyński, K., & Kozłowska, E. (2024) · Genes · doi:10.3390/genes15050577 · Cited by 18 · see citing works
“Furthermore, Zhang et al. [25] suggested that the quantity of p53 pulses could predict a cell’s fate—whether it survives or dies.”
BackgroundModeling and controlling the two-phase dynamics of the p53 network: a Boolean network approach
Lin, G., Ao, B., Chen, J., Wang, W., & Di, Z. (2014) · New Journal of Physics · doi:10.1088/1367-2630/16/12/125010 · Cited by 18 · see citing works
“Although continuous dynamical models, as proposed in [8, 18], can describe more details of system, a considerable number of parameters will lead a huge phase space, which is impossible to scan completely.”
BackgroundSelf-citationInterplay between Mdm2 and HIPK2 in the DNA damage response
Zhang, X., Liu, F., & Wang, W. (2014) · Journal of The Royal Society Interface · doi:10.1098/rsif.2014.0319 · Cited by 18 · see citing works
“A series of experimental and theoretical studies have recently probed the dynamics and function of p53 in the DDR [15–17].”
BackgroundSelf-citationMathematical Modeling of p53 Pathways
Kim, E., Kim, J.-Y., & Lee, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205179 · Cited by 17 · see citing works
“Mathematical models that integrated ODE models for cell cycle and DNA damage network predicted the role of p53 in determining immediate or sustained cell cycle types [38,39].”
BackgroundDynamics of Posttranslational Modifications of p53
Qing-duan, F., Wu, G., & Liu, Z. (2014) · Computational and Mathematical Methods in Medicine · doi:10.1155/2014/245610 · Cited by 16 · see citing works
“The number of pulses of p53p, which means cell repair, should lie on cell repair or cell apoptosis under different levels of DNA damage [28].”
BackgroundA plausible model for bimodal p53 switch in DNA damage response
Sun, T., & Cui, J. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.01.044 · Cited by 16 · see citing works
Choi, O. R., Ryu, M. S., & Lim, I. K. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.05.014 · Cited by 16 · see citing works
CSB modulates the competition between HIF-1 and p53 upon hypoxia
Ye, X.-W., Zhang, X., & Liu, F. (2019) · Mathematical Biosciences & Engineering · doi:10.3934/mbe.2019262 · Cited by 15 · see citing works
Self-citationDynamic Mechanism for the Transcription Apparatus Orchestrating Reliable Responses to Activators
Wang, Y., Liu, F., & Wang, W. (2012) · Scientific Reports · doi:10.1038/srep00422 · Cited by 15 · see citing works
Self-citationGu, W., Pan, T., Wang, X., Kang, L., Liu, N., Piao, M., & Feng, C. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114866 · Cited by 14 · see citing works
- 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
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