Mathematical model of the gene network of TNFα-induced NF-kappaB activation

被引:0
作者
Guryeva, Ya P. [1 ]
Stepanenko, I. L. [1 ]
Likhoshvai, V. A. [1 ]
机构
[1] Inst Cytol & Genet SB RAS, Novosibirsk, Russia
来源
Proceedings of the Fourth International Conference on Bioinformatics of Genome Regulation and Structure, Vol 2 | 2004年
关键词
gene networks; mathematical modelling; TNF alpha; NF-kappaB; apoptosis;
D O I
暂无
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Motivation: Proinflammatory cytokine TNF alpha (tumor necrosis factor a) induces two important signal pathways: 1) caspase cascade through caspase-8 activation leading to apoptosis, and. 2) NF-kappaB transcriptional factor activation, which regulates expression of the genes necessary for cell survival. To investigate impact of these two concurrent processes on each other we developed a mathematical model for TNF alpha-inducible activation of NF-kappaB. Results: Using published experimental data and GeneNet technology, gene network of TNF alpha-inducible activation of NF-kappaB; was created. Based on developed network and using generalized chemical kinetic method we constructed a mathematical model which consists of 85 blocks and contains 182 constants and 74 dynamic variables. Using computer analysis of hypothetical mutation effect on gene network function, we obtained quantitative data for the effect of the mutations in cellular-inhibitor of apoptosis proteins (IAPs) and adaptor proteins TRAFs and TRADD on caspase-8 inhibition and activation of NF-kappaB.
引用
收藏
页码:64 / 67
页数:4
相关论文
共 6 条
[1]   Characterization and quantitation of NF-κB nuclear translocation induced by interleukin-1 and tumor necrosis factor-α -: Development and use of a high capacity fluorescence cytometric system [J].
Ding, GJF ;
Fischer, PA ;
Boltz, RC ;
Schmidt, JA ;
Colaianne, JJ ;
Gough, A ;
Rubin, RA ;
Miller, DK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (44) :28897-28905
[2]  
Likhoshvai V. A., 2000, COMPUTATIONAL TECHNO, V5, P87
[3]  
LIKHOSHVAI VA, 2002, P 3 INT C BIOINF GEN, V2, P146
[4]   Measuring dynamics of caspase-8 activation in a single living HeLa cell during TNFα-induced apoptosis [J].
Luo, KQ ;
Yu, VC ;
Pu, YM ;
Chang, DC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 304 (02) :217-222
[5]   REL/NF-KAPPA-B/I-KAPPA-B FAMILY - INTIMATE TALES OF ASSOCIATION AND DISSOCIATION [J].
VERMA, IM ;
STEVENSON, JK ;
SCHWARZ, EM ;
VANANTWERP, D ;
MIYAMOTO, S .
GENES & DEVELOPMENT, 1995, 9 (22) :2723-2735
[6]   Identification of NF-κB-regulated genes induced by TNFα utilizing expression profiling and RNA interference [J].
Zhou, A ;
Scoggin, S ;
Gaynor, RB ;
Williams, NS .
ONCOGENE, 2003, 22 (13) :2054-2064