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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2009-12-17
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pubmed:abstractText |
Apoptosis is regulated by several signaling pathways which are extensively linked by crosstalks. Boolean or logical modeling has become a promising approach to capture the qualitative behavior of such complex networks. Here we built a large-scale literature-based Boolean model of the central intrinsic and extrinsic apoptosis pathways as well as pathways connected with them. The model responds to several external stimuli such as Fas ligand, TNF-alpha, UV-B irradiation, interleukin-1beta and insulin. Timescales and multi-value node logic were used and turned out to be indispensable to reproduce the behavior of the apoptotic network. The coherence of the model was experimentally validated. Thereby an UV-B dose-effect is shown for the first time in mouse hepatocytes. Analysis of the model revealed a tight regulation emerging from high connectivity and spanning crosstalks and a particular importance of feedback loops. An unexpected feedback from Smac release to RIP could further increase complex II formation. The introduced Boolean model provides a comprehensive and coherent description of the apoptosis network behavior. It gives new insights into the complex interplay of pro- and antiapoptotic factors and can be easily expanded to other signaling pathways.
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pubmed:commentsCorrections |
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20011108-9729047
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1553-7358
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e1000595
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
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pubmed:year |
2009
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pubmed:articleTitle |
ON/OFF and beyond--a boolean model of apoptosis.
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pubmed:affiliation |
Institute for System Dynamics, University of Stuttgart, Stuttgart, Germany. rebekka.schlatter@isys.uni-stuttgart.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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