Clb3-centered regulations are recurrent across distinct parameter regions in minimal autonomous cell cycle oscillator designs.

Autor: Mondeel TDGA; Systems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.; Centre for Mathematical and Computational Biology, CMCB, University of Surrey, Guildford, UK.; Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands., Ivanov O; Theoretical Research in Evolutionary Life Sciences, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.; Systems, Control and Applied Analysis Group, Johan Bernoulli Institute for Mathematics and Computer Science, University of Groningen, Groningen, The Netherlands., Westerhoff HV; Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.; Molecular Cell Physiology, VU University Amsterdam, Amsterdam, The Netherlands., Liebermeister W; Institute of Biochemistry, Charité Universitätsmedizin Berlin, Berlin, Germany.; Université Paris-Saclay, INRAE, MaIAGE, Jouy en Josas, France., Barberis M; Systems Biology, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK. m.barberis@surrey.ac.uk.; Centre for Mathematical and Computational Biology, CMCB, University of Surrey, Guildford, UK. m.barberis@surrey.ac.uk.; Synthetic Systems Biology and Nuclear Organization, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands. m.barberis@surrey.ac.uk.
Jazyk: angličtina
Zdroj: NPJ systems biology and applications [NPJ Syst Biol Appl] 2020 Apr 03; Vol. 6 (1), pp. 8. Date of Electronic Publication: 2020 Apr 03.
DOI: 10.1038/s41540-020-0125-0
Abstrakt: Some biological networks exhibit oscillations in their components to convert stimuli to time-dependent responses. The eukaryotic cell cycle is such a case, being governed by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with specific timing and guarantee its timely occurrence. Disruption of cyclin/Cdk oscillations could result in dysfunction through reduced cell division. Therefore, it is of interest to capture properties of network designs that exhibit robust oscillations. Here we show that a minimal yeast cell cycle network is able to oscillate autonomously, and that cyclin/Cdk-mediated positive feedback loops (PFLs) and Clb3-centered regulations sustain cyclin/Cdk oscillations, in known and hypothetical network designs. We propose that Clb3-mediated coordination of cyclin/Cdk waves reconciles checkpoint and oscillatory cell cycle models. Considering the evolutionary conservation of the cyclin/Cdk network across eukaryotes, we hypothesize that functional ("healthy") phenotypes require the capacity to oscillate autonomously whereas dysfunctional (potentially "diseased") phenotypes may lack this capacity.
Databáze: MEDLINE
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