MENÜ MENÜ  

cover

Mathematical Modeling of NF-κB and p53 Signaling in the DNA Damage Response

Fabian Konrath

ISBN 978-3-8325-5136-0
251 Seiten, Erscheinungsjahr: 2020
Preis: 55.50 €
Mathematical Modeling of NF-κB and p53 Signaling in the DNA Damage Response
Cells are permanently challenged by DNA damage which can be induced by environmental factors such as UV irradiation or intracellular factors like reactive oxygen species. As damaged DNA can lead to malignant transformations, a complex signaling network termed DNA damage response is activated upon detection of DNA lesions and allows to maintain genomic integrity. The two transcription factors NF-κB and p53 regulate cell fate decisions upon genotoxic stress and therefore play crucial roles in the DNA damage response.

To investigate the regulation of NF-κB activity, a mathematical model of coupled ordinary differential equations was developed and analyzed. The model describes DNA damage-induced activation of NF-$&appa;B and quantitatively reproduces multiple experimental data sets. Analyzing the time-resolved regulation of NF-κB revealed regulatory mechanisms of DNA damage-dependent NF-κB signaling and allowed the evaluation of drug targets inhibiting NF-κB activity.

Further, the interplay of NF-κB and p53 signaling was investigated by developing a mathematical modeling framework to systematically identify interfaces between the NF-κB and p53 network. NF-κB signaling was perturbed and the resulting changes in single cell dynamics of p53 upon genotoxic stress were captured. By fitting a pool of subpopulation-specific ordinary differential equation models to the single cell data, one of the first quantitative p53 models reproducing the heterogeneous dynamics of p53 was developed. Based on the observed changes in p53 dynamics, the results of the modeling framework indicate that NF-κB signaling interferes with the activation and degradation of p53 as well as the degradation of its inhibitor Mdm2.

Taken together, the results in this work give new insights into the regulation of genotoxic NF-κB and p53 signaling and highlight the complexity of their crosstalk.


Wollen auch Sie Ihre Dissertation veröffentlichen?

cover cover cover cover cover cover cover cover cover
Inhaltsverzeichnis (PDF)

Keywords:

  • Modeling
  • Modellierung
  • Signal transduction
  • Signaltransduktion
  • DNA damage
  • DNA-Schädigung
  • NF-κB
  • p53

KAUFOPTIONEN

55.50 €
auf Lager
Versandkostenfrei innerhalb Deutschlands

44.00 €
65.50 €
69.50 €

(D) = innerhalb Deutschlands
(W) = außerhalb Deutschlands

*Sie können das eBook (PDF) entweder einzeln herunterladen oder in Kombination mit dem gedruckten Buch (eBundle) erwerben. Der Erwerb beider Optionen wird über PayPal abgerechnet - zur Nutzung muss aber kein PayPal-Account angelegt werden. Mit dem Erwerb des eBooks bzw. eBundles akzeptieren Sie unsere Lizenzbedingungen für eBooks.

Bei Interesse an Multiuser- oder Campus-Lizenzen (MyLibrary) füllen Sie bitte das Formular aus oder schreiben Sie eine email an order@logos-verlag.de