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Home Search Quick Search Advanced Fulltext Browse Collections Persons My eDoc Session History Login Name: Password: Documentation Help Support Wiki Direct access to document ID:	Institute: MPI für Dynamik komplexer technischer Systeme     Collection: Systems Biology     Display Documents   history 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... Full Text: You have privileges to view the following file(s): 443825_adv_appl_bio_chem.pdf  [2,00 Mb]      The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.