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. 2006 Oct 31;33(1):75–83. doi: 10.1007/s00726-006-0454-3

A dynamic model for the p53 stress response networks under ion radiation

J-P Qi 1, S-H Shao 1, D-D Li 1, G-P Zhou 2
PMCID: PMC7088058  PMID: 17072789

Summary.

P53 controls the cell cycle arrest and cell apoptosis through interaction with the downstream genes and their signal pathways. To stimulate the investigation into the complicated responses of p53 under the circumstance of ion radiation (IR) in the cellular level, a dynamic model for the p53 stress response networks is proposed. The model can be successfully used to simulate the dynamic processes of generating the double-strand breaks (DSBs) and their repairing, ataxia telangiectasia mutated (ATM) activation, as well as the oscillations occurring in the p53-MDM2 feedback loop.

Keywords: Keywords: Cellular networks – p53 – MDM2 – IR – DNA damage – Oscillations

References

  1. Althaus IW, Chou JJ, Gonzales AJ, Diebel MR, Chou KC, Kezdy FJ, Romero DL, Aristoff PA, Tarpley WG, Reusser F. Steady-state kinetic studies with the non-nucleoside HIV-1 reverse transcriptase inhibitor U-87201E. J Biol Chem. 1993a;268:6119–6124. [PubMed] [Google Scholar]
  2. Althaus IW, Gonzales AJ, Chou JJ, Diebel MR, Chou KC, Kezdy FJ, Romero DL, Aristoff PA, Tarpley WG, Reusser F. The quinoline U-78036 is a potent inhibitor of HIV-1 reverse transcriptase. J Biol Chem. 1993b;268:14875–14880. [PubMed] [Google Scholar]
  3. Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature. 2003;421:499–506. doi: 10.1038/nature01368. [DOI] [PubMed] [Google Scholar]
  4. Budman J, Chu G. Processing of DNA for nonhomologous end-joining by cell-free extract. Embo J. 2005;24:849–860. doi: 10.1038/sj.emboj.7600563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chou JJ, Li H, Salvessen GS, Yuan J, Wagner G. Solution structure of BID, an intracellular amplifier of apoptotic signalling. Cell. 1999a;96:615–624. doi: 10.1016/S0092-8674(00)80572-3. [DOI] [PubMed] [Google Scholar]
  6. Chou KC. Low-frequency vibration of DNA molecules. Biochem J. 1984;221:27–31. doi: 10.1042/bj2210027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chou KC. The biological functions of low-frequency phonons: 6. A possible dynamic mechanism of allosteric transition in antibody molecules. Biopolymers. 1987;26:285–295. doi: 10.1002/bip.360260209. [DOI] [PubMed] [Google Scholar]
  8. Chou KC. Review: Low-frequency collective motion in biomacromolecules and its biological functions. Biophys Chem. 1988;30:3–48. doi: 10.1016/0301-4622(88)85002-6. [DOI] [PubMed] [Google Scholar]
  9. Chou KC. Graphical rules in steady and non-steady enzyme kinetics. J Biol Chem. 1989a;264:12074–12079. [PubMed] [Google Scholar]
  10. Chou KC. Low-frequency resonance and cooperativity of hemoglobin. Trends Biochem Sci. 1989b;14:212. doi: 10.1016/0968-0004(89)90026-1. [DOI] [PubMed] [Google Scholar]
  11. Chou KC. Review: Applications of graph theory to enzyme kinetics and protein folding kinetics. Steady and non-steady state systems. Biophys Chem. 1990;35:1–24. doi: 10.1016/0301-4622(90)80056-D. [DOI] [PubMed] [Google Scholar]
  12. Chou KC. Review: Structural bioinformatics and its impact to biomedical science. Curr Med Chem. 2004;11:2105–2134. doi: 10.2174/0929867043364667. [DOI] [PubMed] [Google Scholar]
  13. Chou KC, Chen NY. The biological functions of low-frequency phonons. Sci Sin. 1977;20:447–457. [Google Scholar]
  14. Chou KC, Forsen S. Graphical rules for enzyme-catalyzed rate laws. Biochem J. 1980;187:829–835. doi: 10.1042/bj1870829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chou KC, Jiang SP. Studies on the rate of diffusion-controlled reactions of enzymes. Sci Sin. 1974;17:664–680. [PubMed] [Google Scholar]
  16. Chou KC, Jiang SP, Liu WM, Fee CH. Graph theory of enzyme kinetics: 1. Steady-state reaction system. Sci Sin. 1979;22:341–358. [Google Scholar]
  17. Chou KC, Jones D, Heinrikson RL. Prediction of the tertiary structure and substrate binding site of caspase-8. FEBS Lett. 1997;419:49–54. doi: 10.1016/S0014-5793(97)01246-5. [DOI] [PubMed] [Google Scholar]
  18. Chou KC, Kezdy FJ, Reusser F. Review: steady-state inhibition kinetics of processive nucleic acid polymerases and nucleases. Anal Biochem. 1994a;221:217–230. doi: 10.1006/abio.1994.1405. [DOI] [PubMed] [Google Scholar]
  19. Chou KC, Maggiora GM, Mao B. Quasi-continuum models of twist-like and accordion-like low-frequency motions in DNA. Biophys J. 1989;56:295–305. doi: 10.1016/S0006-3495(89)82676-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Chou KC, Mao B. Collective motion in DNA and its role in drug intercalation. Biopolymers. 1988;27:1795–1815. doi: 10.1002/bip.360271109. [DOI] [PubMed] [Google Scholar]
  21. Chou KC, Tomasselli AG, Heinrikson RL. Prediction of the tertiary structure of a caspase-9/inhibitor complex. FEBS Lett. 2000;470:249–256. doi: 10.1016/S0014-5793(00)01333-8. [DOI] [PubMed] [Google Scholar]
  22. Chou KC, Watenpaugh KD, Heinrikson RL. A model of the complex between cyclin-dependent kinase 5(Cdk5) and the activation domain of neuronal Cdk5 activator. Biochem Biophys Res Commun. 1999b;259:420–428. doi: 10.1006/bbrc.1999.0792. [DOI] [PubMed] [Google Scholar]
  23. Chou KC, Zhang CT. Diagrammatization of codon usage in 339 HIV proteins and its biological implication. AIDS Res Hum Retroviruses. 1992;8:1967–1976. doi: 10.1089/aid.1992.8.1967. [DOI] [PubMed] [Google Scholar]
  24. Chou KC, Zhang CT, Maggiora GM. Solitary wave dynamics as a mechanism for explaining the internal motion during microtubule growth. Biopolymers. 1994b;34:143–153. doi: 10.1002/bip.360340114. [DOI] [PubMed] [Google Scholar]
  25. Chou KC, Zhou GP. Role of the protein outside active site on the diffusion-controlled reaction of enzyme. J Am Chem Soc. 1982;104:1409–1413. doi: 10.1021/ja00369a043. [DOI] [Google Scholar]
  26. Cotes NJ, Sceats MG. Biomolecular reactions with a reactive site on a spherical particle: a Hamiltonian formulation. J Chem Phys. 1988;89:2816–2821. doi: 10.1063/1.454984. [DOI] [Google Scholar]
  27. Daboussi F, Dumay A, Delacote F, Lopez BS. DNA double-strand break repair signalling: the case of RAD51 post-translational regulation. Cell Signal. 2002;14:969–975. doi: 10.1016/S0898-6568(02)00052-9. [DOI] [PubMed] [Google Scholar]
  28. Gao L, Ding YS, Dai H, Shao SH, Huang ZD, Chou KC. A novel fingerprint map for detecting SARS-CoV. J Pharm Biomed Anal. 2006;41:246–250. doi: 10.1016/j.jpba.2005.09.031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Han WG. The influence of dipole-dipole interaction on the low-frequency vibrations in alpha-helix proteins. Biophys Chem. 1992;43:169–173. doi: 10.1016/0301-4622(92)80031-Y. [DOI] [Google Scholar]
  30. Han WG, Wang CD. The vibrational normal modes of beta-barrels in an IgG antibody molecule. Biophys Chem. 1992;44:29–45. doi: 10.1016/0301-4622(92)85033-Z. [DOI] [PubMed] [Google Scholar]
  31. King EL, Altman C. A schematic method of deriving the rate laws for enzyme-catalyzed reactions. J Phys Chem. 1956;60:1375–1378. doi: 10.1021/j150544a010. [DOI] [Google Scholar]
  32. Kohn KW, Pommier Y. Molecular interaction map of the p53 and Mdm2 logic elements, which control the Off-On switch of p53 in response to DNA damage. Biochem Biophys Res Commun. 2005;331:816–827. doi: 10.1016/j.bbrc.2005.03.186. [DOI] [PubMed] [Google Scholar]
  33. Kuzmic P, Ng KY, Heath TD. Mixtures of tight-binding enzyme inhibitors. Kinetic analysis by a recursive rate equation. Anal Biochem. 1992;200:68–73. doi: 10.1016/0003-2697(92)90278-F. [DOI] [PubMed] [Google Scholar]
  34. Lahav G, Rosenfeld N, Sigal A, Geva-Zatorsky N, Levine AJ, Elowitz MB, Alon U. Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat Genet. 2004;36:147–150. doi: 10.1038/ng1293. [DOI] [PubMed] [Google Scholar]
  35. Lev Bar-Or R, Maya R, Segel LA, Alon U, Levine AJ, Oren M. Generation of oscillations by the p53-Mdm2 feedback loop: a theoretical and experimental study. Proc Natl Acad Sci USA. 2000;97:11250–11255. doi: 10.1073/pnas.210171597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lin SX, Neet KE. Demonstration of a slow conformational change in liver glucokinase by fluorescence spectroscopy. J Biol Chem. 1990;265:9670–9675. [PubMed] [Google Scholar]
  37. Ma L, Wagner J, Rice JJ, Hu W, Levine AJ, Stolovitzky GA. A plausible model for the digital response of p53 to DNA damage. Proc Natl Acad Sci USA. 2005;102:14266–14271. doi: 10.1073/pnas.0501352102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Magne N, Toillon RA, Bottero V, Didelot C, Houtte PV, Gerard JP, Peyron JF. NF-kappaB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Lett. 2006;231:158–168. doi: 10.1016/j.canlet.2005.01.022. [DOI] [PubMed] [Google Scholar]
  39. Martel P. Biophysical aspects of neutron scattering from vibrational modes of proteins. Prog Biophys Mol Biol. 1992;57:129–179. doi: 10.1016/0079-6107(92)90023-Y. [DOI] [PubMed] [Google Scholar]
  40. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ. 2003;10:431–442. doi: 10.1038/sj.cdd.4401183. [DOI] [PubMed] [Google Scholar]
  41. Pauklin S, Kristjuhan A, Maimets T, Jaks V. ARF and ATM/ATR cooperate in p53-mediated apoptosis upon oncogenic stress. Biochem Biophys Res Commun. 2005;334:386–394. doi: 10.1016/j.bbrc.2005.06.097. [DOI] [PubMed] [Google Scholar]
  42. Perez CA, Purdy JA. Treatment planning in radiation oncology and impact on outcome of therapy. Rays. 1998;23:385–426. [PubMed] [Google Scholar]
  43. Rapp A, Greulich KO. After double-strand break induction by UV-A, homologous recombination and nonhomologous end joining cooperate at the same DSB if both systems are available. J Cell Sci. 2004;117:4935–4945. doi: 10.1242/jcs.01355. [DOI] [PubMed] [Google Scholar]
  44. Ritter MA, Gilchrist KW, Voytovich M, Chappell RJ, Verhoven BM. The role of p53 in radiation therapy outcomes for favorable-to-intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2002;53:574–580. doi: 10.1016/S0360-3016(02)02781-5. [DOI] [PubMed] [Google Scholar]
  45. Rothkamm K, Kruger I, Thompson LH, Lobrich M. Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol. 2003;23:5706–5715. doi: 10.1128/MCB.23.16.5706-5715.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sinkala Z. Soliton/exciton transport in proteins. J Theor Biol. 2006;241:919–927. doi: 10.1016/j.jtbi.2006.01.028. [DOI] [PubMed] [Google Scholar]
  47. Sobell HM, Banerjee A, Lozansky ED, Zhou GP, Chou KC (1983) The role of low-frequency (acoustic) phonons in determining the premelting and melting behaviors of DNA. In: Clementi E, Sarma RH (eds) Structure and dynamics: nucleic acids and proteins. New York, pp 181–195
  48. Tyson JJ. Models of cell cycle control in eukaryotes. J Biotechnol. 1999;71:239–244. doi: 10.1016/S0168-1656(99)00027-9. [DOI] [PubMed] [Google Scholar]
  49. Tyson JJ, Novak B. Regulation of the eukaryotic cell cycle: molecular antagonism, hysteresis, and irreversible transitions. J Theor Biol. 2001;210:249–263. doi: 10.1006/jtbi.2001.2293. [DOI] [PubMed] [Google Scholar]
  50. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–310. doi: 10.1038/35042675. [DOI] [PubMed] [Google Scholar]
  51. Wang M, Yao JS, Huang ZD, Xu ZJ, Liu GP, Zhao HY, Wang XY, Yang J, Zhu YS, Chou KC. A new nucleotide-composition based fingerprint of SARS-CoV with visualization analysis. Med Chem. 2005;1:39–47. doi: 10.2174/1573406053402505. [DOI] [PubMed] [Google Scholar]
  52. Weller M. Predicting response to cancer chemotherapy: the role of p53. Cell Tissue Res. 1998;292:435–445. doi: 10.1007/s004410051072. [DOI] [PubMed] [Google Scholar]
  53. Xiao X, Shao S, Ding Y, Huang Z, Chen X, Chou KC. An application of gene comparative image for predicting the effect on replication ratio by HBV virus gene missense mutation. J Theor Biol. 2005;235:555–565. doi: 10.1016/j.jtbi.2005.02.008. [DOI] [PubMed] [Google Scholar]
  54. Xiao X, Shao SH, Chou KC. A probability cellular automaton model for hepatitis B viral infections. Biochem Biophys Res Commun. 2006;342:605–610. doi: 10.1016/j.bbrc.2006.01.166. [DOI] [PubMed] [Google Scholar]
  55. Zhang CT, Chou KC. Analysis of codon usage in 1562 E. Coli protein coding sequences. J Mol Biol. 1994;238:1–8. doi: 10.1006/jmbi.1994.1263. [DOI] [PubMed] [Google Scholar]
  56. Zhang CT, Chou KC. An analysis of base frequencies in the anti-sense strands corresponding to the 180 human protein coding sequences. Amino Acids. 1996;10:253–262. doi: 10.1007/BF00807327. [DOI] [PubMed] [Google Scholar]
  57. Zhou G, Wong MT, Zhou GQ. Diffusion-controlled reactions of enzymes. An approximate analytic solution of Chou’s model. Biophys Chem. 1983;18:125–132. doi: 10.1016/0301-4622(83)85006-6. [DOI] [PubMed] [Google Scholar]
  58. Zhou GP. Biological functions of soliton and extra electron motion in DNA structure. Phys Scripta. 1989;40:698–701. doi: 10.1088/0031-8949/40/5/021. [DOI] [Google Scholar]
  59. Zhou GP, Deng MH. An extension of Chou’s graphical rules for deriving enzyme kinetic equations to system involving parallel reaction pathways. Biochem J. 1984;222:169–176. doi: 10.1042/bj2220169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Zhou GQ, Zhong WZ. Diffusion-controlled reactions of enzymes. A comparison between Chou’s model and Alberty-Hammes-Eigen’s model. Eur J Biochem. 1982;128:383–387. doi: 10.1111/j.1432-1033.1982.tb06976.x. [DOI] [PubMed] [Google Scholar]

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