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          Institute: MPI für Dynamik komplexer technischer Systeme     Collection: Systems Biology     Display Documents



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ID: 443825.0, MPI für Dynamik komplexer technischer Systeme / Systems Biology
Logical network of genotoxic stress-induced NF-kB signal transduction predicts putative target structures for therapeutic intervention strategies
Authors:Poltz, R.; Franke, R.; Schweitzer, K.; Klamt, S.; Gilles, E. D.; Naumann, M.
Language:English
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Advances and Applications in Bioinformatics and Chemistry
Volume:2
Start Page:125
End Page:138
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Genotoxic stress is induced by a broad range of DNA-damaging agents and could lead to a variety of human diseases including cancer. DNA damage is also therapeutically induced for cancer treatment with the aim to eliminate tumor cells. However, the effectiveness of radio- and chemotherapy is strongly hampered by tumor cell resistance. A major reason for radio- and chemotherapeutic resistances is the simultaneous activation of cell survival pathways resulting in the activation of the transcription factor nuclear factor-kappa B (NF-κB). Here, we present a Boolean network model of the NF-κB signal transduction induced by genotoxic stress in epithelial cells. For the representation and analysis of the model, we used the formalism of logical interaction hypergraphs. Model reconstruction was based on a careful meta-analysis of published data. By calculating minimal intervention sets, we identified p53-induced protein with a death domain (PIDD), receptor-interacting protein 1 (RIP1), and protein inhibitor of activated STAT y (PIASy) as putative therapeutic targets to abrogate NF-κB activation resulting in apoptosis. Targeting these structures therapeutically may potentiate the effectiveness of radio- and chemotherapy. Thus, the presented model allows a better understanding of the signal transduction in tumor cells and provides candidates as new therapeutic target structures.

© 2009 Poltz et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited. [accessed February 5th, 2010]
External Publication Status:published
Document Type:Article
Communicated by:Ernst-Dieter Gilles
Affiliations:MPI für Dynamik komplexer technischer Systeme/Systems Biology
MPI für Dynamik komplexer technischer Systeme
External Affiliations:Otto von Guericke University
Institute of Experimental Internal Medicine
Magdeburg
Identifiers:LOCALID:OA 443825
URL:http://www.dovepress.com/logical-network-of-genoto...
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