Understanding the <scp>mTOR</scp> signaling pathway via mathematical modeling

  • Nurgazy Sulaimanov
    Department of Electrical Engineering and Information Technology Technische Universität Darmstadt Darmstadt Germany
  • Martin Klose
    Systems Biology of the Cellular Microenvironment at the DKFZ Partner Site Freiburg ‐ Member of the German Cancer Consortium, Institute of Molecular Medicine and Cell Research Albert‐Ludwigs‐University Freiburg Freiburg Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Hauke Busch
    Systems Biology of the Cellular Microenvironment at the DKFZ Partner Site Freiburg ‐ Member of the German Cancer Consortium, Institute of Molecular Medicine and Cell Research Albert‐Ludwigs‐University Freiburg Freiburg Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Melanie Boerries
    Systems Biology of the Cellular Microenvironment at the DKFZ Partner Site Freiburg ‐ Member of the German Cancer Consortium, Institute of Molecular Medicine and Cell Research Albert‐Ludwigs‐University Freiburg Freiburg Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany

説明

<jats:p>The mechanistic target of rapamycin (<jats:styled-content style="fixed-case">mTOR</jats:styled-content>) is a central regulatory pathway that integrates a variety of environmental cues to control cellular growth and homeostasis by intricate molecular feedbacks. In spite of extensive knowledge about its components, the molecular understanding of how these function together in space and time remains poor and there is a need for Systems Biology approaches to perform systematic analyses. In this work, we review the recent progress how the combined efforts of mathematical models and quantitative experiments shed new light on our understanding of the <jats:styled-content style="fixed-case">mTOR</jats:styled-content> signaling pathway. In particular, we discuss the modeling concepts applied in <jats:styled-content style="fixed-case">mTOR</jats:styled-content> signaling, the role of multiple feedbacks and the crosstalk mechanisms of <jats:styled-content style="fixed-case">mTOR</jats:styled-content> with other signaling pathways. We also discuss the contribution of principles from information and network theory that have been successfully applied in dissecting design principles of the <jats:styled-content style="fixed-case">mTOR</jats:styled-content> signaling network. We finally propose to classify the <jats:styled-content style="fixed-case">mTOR</jats:styled-content> models in terms of the time scale and network complexity, and outline the importance of the classification toward the development of highly comprehensive and predictive models. <jats:italic>WIREs Syst Biol Med</jats:italic> 2017, 9:e1379. doi: 10.1002/wsbm.1379</jats:p><jats:p>This article is categorized under: <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Biological Mechanisms > Cell Signaling</jats:p></jats:list-item> <jats:list-item><jats:p>Models of Systems Properties and Processes > Mechanistic Models</jats:p></jats:list-item> </jats:list></jats:p>

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