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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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