The p53 network and its control via MDM2 inhibitors: insights from a dynamic model

被引:2
作者
Lillacci, Gabriele [1 ]
Boccadoro, Mauro [1 ]
Valigi, Paolo [1 ]
机构
[1] Univ Perugia, Dipartimento Ingn Elettron & Informaz, I-06125 Perugia, Italy
来源
PROCEEDINGS OF THE 45TH IEEE CONFERENCE ON DECISION AND CONTROL, VOLS 1-14 | 2006年
关键词
D O I
10.1109/CDC.2006.376908
中图分类号
TP [自动化技术、计算机技术];
学科分类号
0812 ;
摘要
The p53 gene plays a critical role in the cell's response to DNA damage. In this paper we propose a new dynamic model of p53 activation in response to a particular type of damage (double strand brakes), known to be the most important kind of lesion through which ionizing radiation induces cancer and hereditary diseases. Then we try to sum up the main features of this network resulting from experimental observations and use the model to show the correlation that exists between the periodic behavior of this system and its healthy operation. Finally, we apply the model to study the mechanism of action of a particular class of drugs which offer a new interesting research perspective to cancer therapy.
引用
收藏
页码:2110 / 2115
页数:6
相关论文
共 14 条
  • [1] DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Bakkenist, CJ
    Kastan, MB
    [J]. NATURE, 2003, 421 (6922) : 499 - 506
  • [2] Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study
    Bar-Or, RL
    Maya, R
    Segel, LA
    Alon, U
    Levine, AJ
    Oren, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (21) : 11250 - 11255
  • [3] DNA damage and repair
    Friedberg, EC
    [J]. NATURE, 2003, 421 (6921) : 436 - 440
  • [4] RESCUE OF EMBRYONIC LETHALITY IN MDM2-DEFICIENT MICE BY ABSENCE OF P53
    JONES, SN
    ROE, AE
    DONEHOWER, LA
    BRADLEY, A
    [J]. NATURE, 1995, 378 (6553) : 206 - 208
  • [5] Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19(ARF)
    Kamijo, T
    Zindy, F
    Roussel, MF
    Quelle, DE
    Downing, JR
    Ashmun, RA
    Grosveld, G
    Sherr, CJ
    [J]. CELL, 1997, 91 (05) : 649 - 659
  • [6] Dynamics of the p53-Mdm2 feedback loop in individual cells
    Lahav, G
    Rosenfeld, N
    Sigal, A
    Geva-Zatorsky, N
    Levine, AJ
    Elowitz, MB
    Alon, U
    [J]. NATURE GENETICS, 2004, 36 (02) : 147 - 150
  • [7] A plausible model for the digital response of p53 to DNA damage
    Ma, L
    Wagner, J
    Rice, JJ
    Hu, WW
    Levine, AJ
    Stolovitzky, GA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (40) : 14266 - 14271
  • [8] Possible oscillatory behavior in p53-mdm2 interaction computer simulation
    Mihalas, GI
    Simon, Z
    Balea, G
    Popa, E
    [J]. JOURNAL OF BIOLOGICAL SYSTEMS, 2000, 8 (01) : 21 - 29
  • [9] Oscillatory expression of Hes1, p53, and NF-κB driven by transcriptional time delays
    Monk, NAM
    [J]. CURRENT BIOLOGY, 2003, 13 (16) : 1409 - 1413
  • [10] Thompson J.M.T., 2002, NONLINEAR DYNAMICS C