Cristin-resultat-ID: 732743
Sist endret: 19. mars 2011 09:40
NVI-rapporteringsår: 2010
Resultat
Vitenskapelig artikkel
2010

Harmonic Oscillations in Homeostatic Controllers: Dynamics of the p53 Regulatory System

Bidragsytere:
  • Ingunn Jolma
  • Xiao Yu Ni
  • L. Rensing og
  • Peter Ruoff

Tidsskrift

Biophysical Journal
ISSN 0006-3495
e-ISSN 1542-0086
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2010
Volum: 98
Hefte: 5
Sider: 743 - 752

Importkilder

Isi-ID: 000275232100001

Beskrivelse Beskrivelse

Tittel

Harmonic Oscillations in Homeostatic Controllers: Dynamics of the p53 Regulatory System

Sammendrag

Homeostatic mechanisms are essential for the protection and adaptation of organisms in a changing and challenging environment. Previously, we have described molecular mechanisms that lead to robust homeostasis/adaptation under inflow or outflow perturbations. Here we report that harmonic oscillations occur in models of such homeostatic controllers and that a close relationship exists between the control of the p53/Mdm2 system and that of a homeostatic inflow controller. This homeostatic control model of the p53 system provides an explanation why large fluctuations in the amplitude of p53/Mdm2 oscillations may arise as part of the homeostatic regulation of p53 by Mdm2 under DNA-damaging conditions. In the presence of DNA damage p53 is upregulated, but is subject to a tight control by Mdm2 and other factors to avoid a premature apoptotic response of the cell at low DNA damage levels. One of the regulatory steps is the Mdm2-mediated degradation of p53 by the proteasome. Oscillations in the p53/Mdm2 system are considered to be part of a mechanism by which a cell decides between cell cycle arrest/DNA repair and apoptosis. In the homeostatic inflow control model, harmonic oscillations in p53/Mdm2 levels arise when the binding strength of p53 to degradation complexes increases. Due to the harmonic character of the oscillations rapid fluctuating noise can lead, as experimentally observed, to large variations in the amplitude of the oscillation but not in their period, a behavior which has been difficult to simulate by deterministic limit-cycle models. In conclusion, the oscillatory response of homeostatic controllers may provide new insights into the origin and role of oscillations observed in homeostatically controlled molecular networks.

Bidragsytere

Ingunn Westvik Jolma

Bidragsyterens navn vises på dette resultatet som Ingunn Jolma
  • Tilknyttet:
    Forfatter
    ved Institutt for matematikk og fysikk ved Universitetet i Stavanger

Xiaoyu Ni

Bidragsyterens navn vises på dette resultatet som Xiao Yu Ni
  • Tilknyttet:
    Forfatter
    ved Institutt for matematikk og fysikk ved Universitetet i Stavanger

L. Rensing

  • Tilknyttet:
    Forfatter
    ved Universität Bremen

Heinz Peter Ruoff

Bidragsyterens navn vises på dette resultatet som Peter Ruoff
  • Tilknyttet:
    Forfatter
    ved Institutt for matematikk og fysikk ved Universitetet i Stavanger
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