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
Items 101–200 of 252
Complete synchronization of the global coupled dynamical network induced by Poisson noises
Guo, Q., & Wan, F. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188632 · Cited by 14
Dynamics of p53 regulatory network in DNA damage response
Gao, C., & Chen, F. (2020) · Applied Mathematical Modelling · doi:10.1016/j.apm.2020.06.057 · Cited by 14
Disorder, oscillatory dynamics and state switching: the role of c-Myc
Rangarajan, N., Fox, Z., Singh, A., Kulkarni, P., & Govindan Rangarajan, C. (2015) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2015.09.013 · Cited by 14
“Based on these and other observations, Zhang et al. (2009) developed a theoretical model to explain how p53 pulses may determine cell fate.”
InfluentialExploring a minimal two-component p53 model
Sun, T., Yuan, R., Xu, W., Zhu, F., & Shen, P. (2010) · Physical Biology · doi:10.1088/1478-3975/7/3/036008 · Cited by 14
“Later experiments further revealed a dynamic pattern called ‘digital oscillation’ [12], although more recent experiments raised some questions.”
ResultA mathematical analysis of DNA damage induced G2 phase transition
Zhang, L., Cheng, Y., & Liew, K. M. (2013) · Applied Mathematics and Computation · doi:10.1016/j.amc.2013.10.025 · Cited by 13
Ito, S. S., Nakagawa, Y., Matsubayashi, M., Sakaguchi, Y. M., Kobashigawa, S., Matsui, T. K., Nanaura, H., Nakanishi, M., Kitayoshi, F., Kikuchi, S., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013726 · Cited by 12
“5-FU induces unstable conformations in the DNA structure at the S phase, and where too many SSBs are present at stalled replication forks in 5-FU–treated cells, DSBs are induced (9, 10).”
BackgroundEncoding and Decoding of p53 Dynamics in Cellular Response to Stresses
Wang, P., Wang, H., Gao, X., Zhu, H.-X., Zhang, X., Liu, F., & Wang, W. (2023) · Cells · doi:10.3390/cells12030490 · Cited by 13
“That is consistent with the previous experimental observation that apoptosis is really irreversible after “the point of no return” [16,19].”
BackgroundResultInfluentialSelf-citationAttachment-regulated signaling networks in the fibroblast-populated 3D collagen matrix
Carlson, M. A., Smith, L. M., Cordes, C. M., Chao, J., & Eudy, J. D. (2013) · Scientific Reports · doi:10.1038/srep01880 · Cited by 13
Landscape and flux quantify the stochastic transition dynamics for p53 cell fate decision
Ye, L., Song, Z., & Li, C. (2021) · The Journal of Chemical Physics · doi:10.1063/5.0030558 · Cited by 13
Cytoplasmic Protein Serine/Threonine Kinases
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_5 · Cited by 11
Bi, Y., Yang, Z., Zhuge, C., & Lei, J. (2015) · Chaos An Interdisciplinary Journal of Nonlinear Science · doi:10.1063/1.4934967 · Cited by 12
Rewiring drug-activated p53-regulatory network from suppressing to promoting tumorigenesis
Song, W., Wang, J., Yang, Y., Jing, N., Zhang, X., Chen, L., & Wu, J. (2012) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjs029 · Cited by 12
“It is well documented that p53 plays its tumor suppressor roles through triggering either apoptosis or cell-cycle arrest in a transcription-dependent and –independent manner (Vogelstein et al., 2000; Zhang et al., 2009; Levine and Oren, 2009).”
BackgroundSelf-citationOscillatory Dynamics of p53 Genetic Network Induced by Feedback Loops and Time Delays
Wang, C., Liu, H., & Zhou, J. (2019) · IEEE Transactions on NanoBioscience · doi:10.1109/tnb.2019.2924079 · Cited by 12
“Extensive evidences indicated that the cell fate is primarily governed by the levels and pulse numbers of p53 oscillations [8], [20].”
BackgroundTheoretical study on the oscillation mechanism of p53-Mdm2 network
Wang, C., Yan, F., Liu, H., & Zhang, Y. (2018) · International Journal of Biomathematics · doi:10.1142/s1793524518501127 · Cited by 12
Wang, K., Zong, D.-C., Wang, Y., & Wang, P.-X. (2019) · Physica A Statistical Mechanics and its Applications · doi:10.1016/j.physa.2019.122861 · Cited by 12
Theoretical Aspects of Cellular Decision-Making and Information-Processing
Kobayashi, T. J., & Kamimura, A. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-7210-1_16 · Cited by 12
Li, Y., Yi, M., & Zou, X. (2013) · Biophysical Journal · doi:10.1016/j.bpj.2013.03.057 · Cited by 11
“An integrated model of the p53 signaling network was developed to study the entire process from the generation of DNA damage to cell-fate decisions (6,7).”
MethodZhang, C.-J., Xu, H., Sui, X., Chen, L., Chen, B., Lv, H., Wang, S., & Wang, X. (2022) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2022.04.012 · Cited by 11
“The decision between which depends on the DNA damage severity and the cell damage tolerance.(12) Eliminating cells with unrepaired damage by inducing apoptosis is an important tumor suppressor function of the DDR pathway.”
BackgroundMathematical modelling of core regulatory mechanism in p53 protein that activates apoptotic switch
Chong, K. H., Samarasinghe, S., Kulasiri, D., & Zheng, J. (2018) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2018.11.008 · Cited by 11
Vera, J., Nikolov, S. G., Lai, X., Singh, A., & Olaf Wolkenhauer, A. (2011) · IET Systems Biology · doi:10.1049/iet-syb.2010.0080 · Cited by 11
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_2 · Cited by 9
Oscillations Governed by the Incoherent Dynamics in Necroptotic Signaling
Xu, F., Yin, Z., Zhu, L., Jin, J., He, Q., Li, X., & Shuai, J. (2021) · Frontiers in Physics · doi:10.3389/fphy.2021.726638 · Cited by 10
The Future of Computational Chemogenomics
Jacoby, E., & Brown, J. B. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8639-2_15 · Cited by 10
Zois, C. E., Giatromanolaki, A. N., Kainulainen, H., Botaitis, S., Karvinen, S. M., Simopoulos, C. E., Kortsaris, A., Sivridis, E., & Koukourakis, M. I. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.12.024 · Cited by 10
Cytoplasmic Protein Tyrosine Kinases
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_4 · Cited by 8
Stulpinas, A., Imbrasaitė, A., Krestnikova, N., Šarlauskas, J., Čėnas, N., & Kalvelytė, A. V. (2015) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.5b00336 · Cited by 9
Chen, H., Shan, J., Liu, J., Feng, Y., Ke, Y., Qi, W., Liu, W., & Zeng, X. (2020) · Cell Proliferation · doi:10.1111/cpr.12780 · Cited by 9
Cell fate decisions by c-Myc depend on ZBTB5 and p53
Choi, S.-H., Koh, D.-I., Ahn, H., Kim, J. Y., Kim, Y., & Hur, M. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.09.137 · Cited by 9
Intrinsic noise and Hill dynamics in the p53 system
Лю, Б., Yan, S., & Wang, Q. (2010) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2010.10.009 · Cited by 9
Sun, J., Yi, M., Yang, L., Wei, W., Ding, Y., & Jia, Y. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.01.036 · Cited by 8
Guanosine Triphosphatases and Their Regulators
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_9 · Cited by 7
Oscillatory expression and variability in p53 regulatory network
Liu, B., Yan, S., Wang, Q., & Liu, S. (2010) · Physica D Nonlinear Phenomena · doi:10.1016/j.physd.2010.09.004 · Cited by 8
Shi, X., & Reimers, J. R. (2018) · Scientific Reports · doi:10.1038/s41598-018-20466-2 · Cited by 8
Exploring the influence of microRNA miR-34 on p53 dynamics: a numerical study*
Liu, N., Yang, H., & Yang, L. (2021) · Communications in Theoretical Physics · doi:10.1088/1572-9494/abd84c · Cited by 8
Codimension-3 Bifurcation in the p53 Regulatory Network Model
Jiang, C., Zhang, Y., & Wang, W. (2021) · International Journal of Bifurcation and Chaos · doi:10.1142/s0218127421501042 · Cited by 8
Self-citationA common pathway to cancer: Oncogenic mutations abolish p53 oscillations
Xiong, L., & Garfinkel, A. (2022) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2022.06.002 · Cited by 9
Matsuda, S., Murakami, M., Ikeda, Y., Nakagawa, Y., Tsuji, A., & Kitagishi, Y. (2020) · Biomedical Reports · doi:10.3892/br.2020.1317 · Cited by 8
“The genomic integrity is maintained by the cells decision to induce DNA repair or to activate the apoptotic cascade (57).”
BackgroundBi, Y., Liu, Q., Wang, L., Yang, W., & Wu, X. (2020) · International Journal of Bifurcation and Chaos · doi:10.1142/s0218127420501345 · Cited by 8
The network structural entropy for single-cell RNA sequencing data during skin aging
Liu, Z., Lin, H., Li, X., Xue, H., Lu, Y., Xu, F., & Shuai, J. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbae698 · Cited by 6
Su, R., Wang, Q., Hu, Q., Wendurige, Li, K., Wang, C., & Tao, L. (2025) · Biomolecules · doi:10.3390/biom15020282 · Cited by 7
“This alternating dominance of positive and negative feedback may cause periodic oscillations in p53 and MDM2 levels, generating pulses [31].”
InfluentialCircadian Rhythm Regulated by Tumor Suppressor p53 and Time Delay in Unstressed Cells
Wang, C., Liu, H., Miao, Z., & Zhou, J. (2020) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2020.3040368 · Cited by 7
“The results are consistent with experimental observations, indicating that p53 keeps low in normal cells and circadian rhythms are autonomous [36], [37].”
ResultFormal verification confirms the role of p53 protein in cell fate decision mechanism
Mahmoud, E. A., Herajy, M., Ziedan, I., & Shehata, H. I. (2022) · Theory in Biosciences · doi:10.1007/s12064-022-00381-x · Cited by 7
“On the other hand, Casp-3 allows the degradation of p21_c, causing the cell cycle arrest forced termination (Zhang et al. 1999).”
BackgroundMathematical modeling of p53 pulses in G2 phase with DNA damage
Zhang, L., Cheng, Y., & Liew, K. M. (2014) · Applied Mathematics and Computation · doi:10.1016/j.amc.2014.01.120 · Cited by 7
Zhang, L., Cheng, Y., & Liew, K. M. (2014) · Applied Mathematics and Computation · doi:10.1016/j.amc.2014.01.081 · Cited by 7
“With incorporation of ATM, this negative feedback loop leads to an oscillation behavior after a sufficiently strong DNA damage signal [16].”
BackgroundGuthrie, O. W. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.08.010 · Cited by 7
Oscillatory Dynamics of p53-Mdm2 Circuit in Response to DNA Damage Caused by Ionizing Radiation
Zhang, Y., Liu, H., Li, Z., Miao, Z., & Zhou, J. (2019) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2019.2899574 · Cited by 7
“the number of pulses produced by p53 oscillations [21], [26];”
InfluentialDynamic Behavior of p53 Driven by Delay and a Microrna-34a-Mediated Feedback Loop
Gao, C., Liu, H., & Yan, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041271 · Cited by 7
“Tt has been reported that robust oscillations can be accomplished through a combination of negative and positive feedback loops rather than a single negative feedback loop [22,23].”
BackgroundPotential dynamic analysis of tumor suppressor p53 regulated by Wip1 protein*
Liu, N., Wang, D., Liu, H., Yang, H., & Yang, L. (2020) · Chinese Physics B · doi:10.1088/1674-1056/ab84d1 · Cited by 7
The birhythmicity increases the diversity of p53 oscillation induced by DNA damage
Wang, D.-G., Zhou, C.-H., & Zhang, X. (2017) · Chinese Physics B · doi:10.1088/1674-1056/26/12/128709 · Cited by 7
Self-citationOscillatory Dynamics and Regulatory Mechanisms of the p53–Per2 Network in DNA-Damaged Cells
Wang, C., Zhang, Y., Cao, J., & Yang, Z. (2024) · IEEE Transactions on Neural Networks and Learning Systems · doi:10.1109/tnnls.2024.3424784 · Cited by 6
“As DNA damage rises ( S = 2 and S = 9), active p53 increases and triggers oscillations that intend to repair the cell, during which Per2 sustains circadian behavior with a period of approximately 23 h [8].”
Akepogu, J., Jakati, S., Chaurasia, S., & Ramachandran, C. (2024) · Experimental Eye Research · doi:10.1016/j.exer.2024.109901 · Cited by 6
Wang, K., Zong, D.-C., Wang, Y., & Li, S. (2020) · Indian Journal of Physics · doi:10.1007/s12648-020-01874-5 · Cited by 6
Beyond Boolean: Ternary networks and dynamics
Yao, Y., Dong, J., Zhu, J., Huang, L., Pei, D., & Lai, Y. (2022) · Chaos An Interdisciplinary Journal of Nonlinear Science · doi:10.1063/5.0097874 · Cited by 6
A Hill type equation can predict target gene expression driven by p53 pulsing
Shi, X. (2021) · FEBS Open Bio · doi:10.1002/2211-5463.13179 · Cited by 6
Deciphering p53 dynamics and cell fate in DNA damage response using mathematical modeling
Yang, N., Sun, T., & Shen, P. (2020) · Genome Instability & Disease · doi:10.1007/s42764-020-00019-6 · Cited by 6
Liu, M., Chen, S., Yueh, M., Wang, G., Hao, H., & Tukey, R. H. (2015) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2015.08.008 · Cited by 6
“When cell damage is minimal, p53 evokes cell cycle arrest by inducing p21 to promote DNA repair and cell survival, whereas sustained p53 activation in response to high damage levels triggers cellular apoptosis, thus preventing the expansion of damaged cells and protecting normal tissue from neoplastic transformation.(…”
BackgroundDesign principles of gene circuits for longevity
Godoy, P., & Hao, N. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.02.006 · Cited by 5
Murakami, Y., & Takada, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074178 · Cited by 5
Influence of parameter values on the oscillation sensitivities of two p53–Mdm2 models
Samaniego, C. C., Valle, A. R., Ayala‐Charca, G., Villota, E., & Coronado, A. M. (2015) · Systems and Synthetic Biology · doi:10.1007/s11693-015-9173-y · Cited by 5
“2a–d. Similar four species models have been proposed elsewhere (Zhang et al. 2007, 2009; Jolma et al. 2010).”
BackgroundSingh, A. T. K., Evens, A. M., Prachand, S., & Gordon, L. I. (2010) · PubMed · Cited by 5
A mathematical model of stem cell regeneration with epigenetic state transitions
Situ, Q., & Lei, J. (2017) · Mathematical Biosciences & Engineering · doi:10.3934/mbe.2017071 · Cited by 5
“Now, to further simplify the equations, we introduce additional assumptions below: (A2) During cell cycle, cell apoptosis is mainly caused by serious DNA damage, which is mostly dependent on the number of initial damage sites and the activity of the DNA damage response pathways [30, 31, 42].”
MethodTheoretical analysis of the delay on the p53 micronetwork
Wang, D., Liu, N., Yang, H., & Yang, L. (2020) · Advances in Difference Equations · doi:10.1186/s13662-020-02799-3 · Cited by 5
Global dynamics and stability of p53-Mdm2 oscillator mediated by Mdm2 production rate
Yuan-hong, B., Yang, Z., & Xiao-Yan, H. (2016) · Acta Physica Sinica · doi:10.7498/aps.65.028701 · Cited by 5
Oscillatory Behaviors of Delayed p53 Regulatory Network with microRNA 192 in DNA Damage Response
Gao, C., & Chen, F. (2021) · International Journal of Bifurcation and Chaos · doi:10.1142/s0218127421500206 · Cited by 5
Stability and bifurcation analysis of a delayed genetic oscillator model
Gao, C., & Chen, F. (2021) · Nonlinear Dynamics · doi:10.1007/s11071-021-06968-1 · Cited by 5
“In addition, the oscillatory behavior of tumor suppressor p53 in response to DNA damage has been widely studied experimentally and theoretically for developing cell control strategies, thereby providing some clues for the treatment of p53 pathway in tumor therapy [4,22,23,26,40,41,44,45].”
BackgroundModulation of signaling cross-talk between pJNK and pAKT generates optimal apoptotic response
Biswas, S., Tikader, B., Kar, S., & Viswanathan, G. A. (2022) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1010626 · Cited by 5
Oscillation induced by Hopf bifurcation in the p53–Mdm2 feedback module
Gao, C., Ji, J., Yan, F., & Liu, H. (2019) · IET Systems Biology · doi:10.1049/iet-syb.2018.5092 · Cited by 5
“Specifically, cell survival or death can be determined by calculating the number of pulses produced by the p53 oscillation [3, 18].”
BackgroundResultInfluentialRigor of cell fate decision by variable p53 pulses and roles of cooperative gene expression by p53
Murakami, Y., & Takada, S. (2012) · BIOPHYSICS · doi:10.2142/biophysics.8.41 · Cited by 5
“Zhang et al. (2009b) included variability in terms of the initial level of DNA damage and its repair dynamics, while the pulse size was still deterministic and fixed.”
BackgroundRegulation in Cell Cycle via p53 and PTEN Tumor Suppressors
Kitagishi, Y., Matsuda, S., Minami, A., Ono, Y., Nakanishi, A., & Ogura, Y. (2014) · Cancer Studies and Molecular Medicine - Open Journal · doi:10.17140/csmmoj-1-101 · Cited by 4
Mitogen-Activated Protein Kinase Module
Thiriet, M. (2012) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-1-4614-4370-4_6 · Cited by 5
Hyperactive end joining repair mediates resistance to DNA damaging therapy in p53-deficient cellsPreprint
Kumar, R. J., Chao, H. X., Roberts, V., Sullivan, A. R., Shah, S., Simpson, D. A., Feng, W., Wozny, A., Kumar, S., Purvis, J. E., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.01.021253 · Cited by 5
Santos‐Sousa, D., da Rosa, S., & Filippi‐Chiela, E. C. (2025) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2025.112052 · Cited by 5
Coupling switches and oscillators as a means to shape cellular signals in biomolecular systems
Zhou, P., Cai, S., Liu, Z., Chen, L., & Wang, R. (2013) · Chaos Solitons & Fractals · doi:10.1016/j.chaos.2012.11.011 · Cited by 4
Wang, Y., Guo, Z., Chen, X., Zhang, W., Lü, A., & Wang, Y. (2015) · Molecular BioSystems · doi:10.1039/c5mb00304k · Cited by 4
Is DNA repair controlled by a biological logic circuit?
Penketh, P. G. (2022) · Theory in Biosciences · doi:10.1007/s12064-021-00360-8 · Cited by 4
Garcia-Garcia, O. R., Ortiz, R., Moreno-Barbosa, E., D-Kondo, J. N., Faddegon, B., & Ramos‐Méndez, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251810061 · Cited by 4
Dynamical studies of cellular signaling networks in cancers
Li, X., Feng, L., & Jian-Wei, S. (2016) · Acta Physica Sinica · doi:10.7498/aps.65.178704 · Cited by 5
Multiple Time Delays Induced Dynamics of p53 Gene Regulatory Network
Bi, Y., Li, Y., Hou, J., & Liu, Q. (2021) · International Journal of Bifurcation and Chaos · doi:10.1142/s0218127421502345 · Cited by 4
Noise Amplification in Human Tumor Suppression following Gamma Irradiation
Liu, B., Yan, S., & Gao, X. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022487 · Cited by 4
“In two well-studied examples, the p53-Mdm2 regulatory network and the NF-kB signaling pathway, noisy oscillations in the cells following activation signals were studied in the experimental [7–12] and theoretical [13–31] aspects.”
MethodOscillation and bistable switching dynamical behavior of p53 regulated by PTEN upon DNA damage
Liu, N., Yang, H., Li, S., Wang, D., & Yang, L. (2021) · Acta Mechanica Sinica · doi:10.1007/s10409-020-01041-3 · Cited by 4
Jana, S., Mondal, M., Mahale, S. P., Gupta, B., Prasasvi, K. R., Kandasami, L., Jha, N., Chowdhury, A., Santosh, V., Kanduri, C., et al. (2023) · eLife · doi:10.7554/elife.88256 · Cited by 5
“The p53-Mdm2 autoregulatory negative feedback loop controls the extent and duration of p53 response upon DNA damage ( Wu et al., 1993 ; Haupt et al., 1997 ; Kubbutat et al., 1997 ; Zhang et al., 2009 ).”
BackgroundNegative feedback and time delay regulate p53 oscillation in response to DNA damage
Wang, C., Lan, X., Haihong, L., & Zhou, J. (2019) · Chinese Control Conference (CCC) · doi:10.23919/chicc.2019.8865331 · Cited by 3
Gut Microbiota and Cancer Correlates
Malaviya, A., Paari, K. A., Malviya, S., Kondapalli, V. K., Ghosh, A., & Samuel, R. A. (2020) · Springer eBooks · doi:10.1007/978-981-15-8214-1_1 · Cited by 3
Noise-induced bistable switching dynamics through a potential energy landscape
Bi, Y., Yang, Z., Meng, X., & Lu, Q. (2015) · Acta Mechanica Sinica · doi:10.1007/s10409-015-0400-2 · Cited by 3
“Until now these generic models have not considered the mutual activation between two species, even though it is a prevalent phenomenon [15–17].”
BackgroundInvestigation of oscillation accumulation triggered genetic switch in gene regulatory networks
He, Q., & Liu, Z. (2014) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2014.03.017 · Cited by 3
Malekinejad, H., Bull, S., Rahmani, F., & Fink‐Gremmels, J. (2011) · Journal of Equine Veterinary Science · doi:10.1016/j.jevs.2011.08.007 · Cited by 3
“Moreover, there are increasing numbers of reports, which indicate an important role of P53 gene in mediating apoptosis [9,10].”
BackgroundA multi-objective method for optimizing the transittability of complex biomolecular networks
Ayadi, A., Zanni-Merk, C., de Beuvron, F. D. B., & Krichen, S. (2018) · Procedia Computer Science · doi:10.1016/j.procs.2018.07.285 · Cited by 3
A simplified dynamic model for the p53-Mdm2 feedback loop
Shi, X., Qin, K., Liu, Z., & Zheng, Y. (2013) · International Conference on Control and Automation · doi:10.1109/icca.2013.6565180 · Cited by 3
“The non-delayed dynamic model by a negative feedback loop coupled with a positive feedback loop can also produce sustained oscillations [8].”
BackgroundMa, A., & Dai, X. (2019) · Interdisciplinary Sciences Computational Life Sciences · doi:10.1007/s12539-019-00332-z · Cited by 3
Malik, M. Z., DASHTI, M. H., Jangid, A., Channanath, A. M., John, S. E., Singh, R. K. B., Al‐Mulla, F., & Thanaraj, T. A. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbae706 · Cited by 2
“…survival by inducing p21 and halting the cell cycle, while high levels of damage lead to sustained p53 pulses that trigger apoptosis via p53AIP1 [25]. p53 governs cell fate through a two-phase response, where pulsatile activation leads to cell cycle arrest and,if DNA damage is irreparable, a…”
Delay Hill dynamics in regulatory biological systems
Liu, B., Yan, S., & Wang, Q. (2010) · Molecular BioSystems · doi:10.1039/c0mb00133c · Cited by 2
Stability and bifurcation analyses of p53 gene regulatory network with time delay
Hou, J., Liu, Q., Yang, H., Wang, L., & Bi, Y. (2022) · Electronic Research Archive · doi:10.3934/era.2022045 · Cited by 2
“More interestingly, the oscillation dynamics of p53 may initiate cell cycle arrest or apoptosis depending on the number of p53 pulses [7,8].”
BackgroundMethodDynamical Aspects of Apoptosis
Bensussen, A., & Daz, J. (2012) · InTech eBooks · doi:10.5772/32570 · Cited by 2
“This could explain why after a long period of time if the cell is not repaired, it dies (Zhang et al., 2009; Yoda et al., 2001; Robinson et al., 2008; Shreeram et al., 2006; Wang et al., 2007; Bergamaschi et al., 2004; Braithwaite, 2006; Green and Kroemer, 2009; Toledo and Wahl, 2006; Liu et al.,…”
BackgroundCellular Response to Irradiation
Liu, B., & Yan, S. (2011) · Communications in Theoretical Physics · doi:10.1088/0253-6102/55/5/34 · Cited by 2
Modeling the heterogeneity of p53 dynamics in DNA damage response
Wu, W., Sun, W., & Sun, T. (2015) · Journal of Bioinformatics and Computational Biology · doi:10.1142/s0219720016500013 · Cited by 2
Information Processing and Integration with Intracellular Dynamics Near Critical Point
Kamimura, A., & Kobayashi, T. J. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00203 · Cited by 2
“At the individual level, examples include differentiation, metabolic switch, apoptosis, and chemotaxis (Blake et al., 2003, 2006; Ueda and Shibata, 2007; Fraser and Kaern, 2009; Macarthur et al., 2009; Zhang et al., 2009).”
BackgroundBRCA1 involved in regulation of Bcl-2 expression and apoptosis susceptibility to ionizing radiation
Wang, Y., Wang, B., Zhang, H., Li, N., Tanaka, K., Zhou, X., Chen, R., & Zhang, X. (2011) · Science China Physics Mechanics and Astronomy · doi:10.1007/s11433-011-4264-6 · Cited by 2
Self-citationContribution of time delays to p53 oscillation in DNA damage response
Wang, C., Liu, H., & Zhou, J. (2019) · IET Systems Biology · doi:10.1049/iet-syb.2019.0006 · Cited by 2
Intrinsic fluctuation and susceptibility in somatic cell reprogramming process
Shen, J. G., Zhang, X., Li, Q., Wang, X., Zhao, Y., & Jia, Y. (2019) · Chinese Physics B · doi:10.1088/1674-1056/28/4/040503 · Cited by 2
Self-citationOscillatory behavior of p53-Mdm2 system driven by transcriptional and translational time delays
Gao, C., Liu, H., Liu, Z., Zhang, Y., & Yan, F. (2020) · International Journal of Biomathematics · doi:10.1142/s1793524520500345 · Cited by 2
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
