A simple model of NF-κB dynamics reproduces experimental observations

被引:18
作者
Zambrano, Samuel [1 ]
Bianchi, Marco E. [1 ]
Agresti, Alessandra [1 ]
机构
[1] San Raffaele Univ, I-20132 Milan, Italy
关键词
Mathematical modeling; Signalling pathways; Transcription factor dynamics; Oscillations; TEMPORAL CONTROL; DNA-BINDING; OSCILLATIONS; EXPRESSION; RESPONSES;
D O I
10.1016/j.jtbi.2014.01.015
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mathematical modeling of the NF-kappa B oscillations has attracted considerable attention in recent times, but there is a lack of simple models in the literature that can capture the main features of the dynamics of this important transcription factor. For this reason we propose a simple model that summarizes the key steps of the NF-kappa B pathway. We show that the resulting 5-dimensional dynamical system can reproduce different phenomena observed in experiments. Our model can display smooth and spiky oscillations in the amount of nuclear NF-kappa B and can reproduce the variety of dynamics observed when different stimulations such as TNF-alpha and LPS are used. Furthermore we show that the model can be easily extended to reproduce the expression of early, intermediate and late genes upon stimulation. As a final example we show that our simple model can mimic the different transcriptional outputs observed when cells are treated with two different drugs leading to nuclear localization of NF-kappa B: Leptomycin B and Cycloheximide. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:44 / 53
页数:10
相关论文
共 32 条
[1]  
Alon U, 2007, INTRO SYSTEMS BIOL
[2]  
ARENZANASEISDEDOS F, 1995, MOL CELL BIOL, V15, P2689
[3]   Pulsatile Stimulation Determines Timing and Specificity of NF-κB-Dependent Transcription [J].
Ashall, Louise ;
Horton, Caroline A. ;
Nelson, David E. ;
Paszek, Pawel ;
Harper, Claire V. ;
Sillitoe, Kate ;
Ryan, Sheila ;
Spiller, David G. ;
Unitt, John F. ;
Broomhead, David S. ;
Kell, Douglas B. ;
Rand, David A. ;
See, Violaine ;
White, Michael R. H. .
SCIENCE, 2009, 324 (5924) :242-246
[4]  
Basak S., 2011, IMMUNOL REV, V221-238, P153
[5]   Modeling and Analysis of Mass-Action Kinetics NONNEGATIVITY, REALIZABILITY, REDUCIBILITY, AND SEMISTABILITY [J].
Chellaboina, Vijaysekhar ;
Bhat, Sanjay P. ;
Haddad, Wassim M. ;
Bernstein, Dennis S. .
IEEE CONTROL SYSTEMS MAGAZINE, 2009, 29 (04) :60-78
[6]   Eukaryotic transcriptional dynamics: from single molecules to cell populations [J].
Coulon, Antoine ;
Chow, Carson C. ;
Singer, Robert H. ;
Larson, Daniel R. .
NATURE REVIEWS GENETICS, 2013, 14 (08) :572-584
[7]   Oscillations and variability in the p53 system [J].
Geva-Zatorsky, Naama ;
Rosenfeld, Nitzan ;
Itzkovitz, Shalev ;
Milo, Ron ;
Sigal, Alex ;
Dekel, Erez ;
Yarnitzky, Talia ;
Liron, Yuvalal ;
Polak, Paz ;
Lahav, Galit ;
Alon, Uri .
MOLECULAR SYSTEMS BIOLOGY, 2006, 2 (1) :13P
[8]   Noncooperative Interactions between Transcription Factors and Clustered DNA Binding Sites Enable Graded Transcriptional Responses to Environmental Inputs [J].
Giorgetti, Luca ;
Siggers, Trevor ;
Tiana, Guido ;
Caprara, Greta ;
Notarbartolo, Samuele ;
Corona, Teresa ;
Pasparakis, Manolis ;
Milani, Paolo ;
Bulyk, Martha L. ;
Natoli, Gioacchino .
MOLECULAR CELL, 2010, 37 (03) :418-428
[9]  
Guckenheimer J., 2013, NONLINEAR OSCILLATIO, V42
[10]   RNA splicing regulates the temporal order of TNF-induced gene expression [J].
Hao, Shengli ;
Baltimore, David .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (29) :11934-11939