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An Investigation of Signal Transduction and Irreversible Decision Making Through Monostable and Bistable Switches

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A Systems Theoretic Approach to Systems and Synthetic Biology II: Analysis and Design of Cellular Systems
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Abstract

Highly nonlinear signal transduction is ubiquitous in cell signalling pathways with switch-like behaviour encountered repeatedly. Monostable and bistable switches represent distinct basic switches which are encountered. A number of contexts in cellular signalling (e.g. apopotosis and cell cycle) involve essentially irreversible transitions and decision making. In this article we examine signal transduction through prototypical monostable and bistable switches with a view towards understanding how irreversible signal transduction may occur through them and also examine the similarities and differences in signal transduction and decision making to classes of experimentally employed inputs. The study provides insights into how irreversible transitions may be orchestrated through different switches in cell signalling, the underlying design characteristics, capabilities and constraints involved, and the extent to which these switches can be distinguished based on irreversible decision making to experimentally available classes of inputs.

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References

  1. Albeck JG, Burke JM, Spencer SL, Lauffenburger DA, Sorger PK (2008) Modeling a snap-action, variable-delay switch controlling extrinsic cell death. PLoS Biol 6:2831–2852

    Article  CAS  PubMed  Google Scholar 

  2. Bhalla U, Iyengar R (1999) Emergent properties of networks of biological signaling pathways. Science 283:381–387

    Article  CAS  PubMed  Google Scholar 

  3. Eissing T, Conzelmann H, Gilles ED, Allgower F, Bullinger E, Scheurich P (2004) Bistability analyses of a caspase activation model for receptor-induced apoptosis. J Biol Chem 279:36892–36897

    Article  CAS  PubMed  Google Scholar 

  4. Ferrell JE, Xiong W (2001) Bistability in cell signaling: how to make continuous processes discontinuous, and reversible processes irreversible. Chaos 11:227–236

    Article  CAS  PubMed  Google Scholar 

  5. Goldbeter A, Koshland DE (1981) An amplified sensitivity arising from covalent modification in biological systems. Proc Natl Acad Sci USA 78:6840–6844

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Gu C, Zhang J, Chen Y, Lei J (2011) A trigger model of apoptosis induced by tumor necrosis factor signaling. BMC Syst Biol 5(Suppl 1):S13

    Article  PubMed Central  PubMed  Google Scholar 

  7. Huang C, Ferrell J (1996) Ultrasensitivity in the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA 93:10078–10083

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Liu C, Krishnan J, Xu XY (2011) A systems-based mathematical modelling framework for investigating the effect of drugs on solid tumours. Theor Biol Med Model 8:45

    Article  PubMed Central  PubMed  Google Scholar 

  9. Markevich NI, Hoek JB, Kholodenko BN (2004) Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. J Cell Biol 164:353–359

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Novak B, Tyson JJ, Gyorffy B, Csikasz-Nagy A (2007) Irreversible cell-cycle transitions are due to systems-level feedback. Nat Cell Biol 9:724–728

    Article  CAS  PubMed  Google Scholar 

  11. Schittler D, Hasenauer J, Allgower F, Waldherr S (2010) Cell differentiation modeled via a coupled two-switch regulatory network. Chaos 20

    Google Scholar 

  12. Seaton D, Krishnan J (2011a) A modular systems approach to elucidating the interaction of adaptive and monostable and bistable threshold modules. IET Syst Biol 5:81–94

    Article  CAS  PubMed  Google Scholar 

  13. Seaton D, Krishnan J (2011b) The coupling of pathways and processes through shared components. BMC Syst Biol 5:103

    Article  PubMed Central  PubMed  Google Scholar 

  14. Thomson M, Gunawardena J (2009) Unlimited multistability in multisite phosphorylation systems. Nature 460:274–277

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Varedi KSM, Ventura AC, Merajver SD, Lin XN (2010) Multisite phosphorylation provides an effective and flexible mechanism for switch-like protein degradation. PLoS One 5:e14029

    Google Scholar 

  16. Yao G, Lee TJ, Mori S, Nevins JR, You L (2008) A bistable Rb-E2F switch underlies the restriction point. Nat Cell Biol 10:476–482

    Article  CAS  PubMed  Google Scholar 

  17. Zhang T, Brazhnik P, Tyson J (2009) Computational analysis of dynamical responses to the intrinsic pathway of programmed cell death. Biophys J 97:415–434

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Correspondence to J. Krishnan .

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Krishnan, J., Liu, C. (2014). An Investigation of Signal Transduction and Irreversible Decision Making Through Monostable and Bistable Switches. In: Kulkarni, V., Stan, GB., Raman, K. (eds) A Systems Theoretic Approach to Systems and Synthetic Biology II: Analysis and Design of Cellular Systems. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9047-5_9

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