A model of yeast cell‐cycle regulation based on multisite phosphorylation

Barik, Debashis; Baumann, William T.; Paul, Mark; Novák, Béla; Tyson, John J.

doi:10.1038/msb.2010.55

Cited by 103 publications

(143 citation statements)

References 74 publications

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“…Mutation of phosphorylated serine and threonine residues to alanine is functionally similar to the dephosphorylated state (58). The clustering of 30 phosphosites in the Med15 C terminus suggested that combinatorial phosphorylation on multiple sites affect biological outcome (59,60) as was shown for cell cycle control (61) and for transcription regulation (62).…”

Section: Med15 Phosphosites Contribute To Suppression Of Stress-inducmentioning

confidence: 82%

Mediator Phosphorylation Prevents Stress Response Transcription During Non-stress Conditions

Miller

Matić

Maier

et al. 2012

Journal of Biological Chemistry

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Background: Mediator is a general coactivator complex for regulated RNA polymerase II transcription. Results: Mediator is phosphorylated on most subunits, and phosphorylation can contribute to function. Conclusion: Post-translational modifications of a transcription coactivator can contribute to its function in gene regulation. Significance: Transcription coactivators can be strongly modified post-translationally, and this can contribute to function.

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Section: Med15 Phosphosites Contribute To Suppression Of Stress-inducmentioning

confidence: 82%

Mediator Phosphorylation Prevents Stress Response Transcription During Non-stress Conditions

Miller

Matić

Maier

et al. 2012

Journal of Biological Chemistry

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“…One is for the bistable switch motif described in Section 2. The other is a more complete cell cycle model of budding yeast involving multiple phosphorylation states that was recently developed by John Tyson's group (Barik et al 2010). …”

Section: Stochastic Modeling and Simulation Of Multistate Systemsmentioning

confidence: 99%

“…However, they failed to capture the intrinsic noise that is caused by the stochastic effects of the low copy numbers of some species. Recently Tyson's group developed a stochastic model for the budding yeast cell cycle by integrating several functional biochemical motifs (Barik et al 2010). These motifs are based on multiple site phosphorylation, which has been discovered to generate nonlinear dynamics (Qu et al 2003) and form bistable switches.…”

Section: Budding Yeast Cell Cycle Modelmentioning

confidence: 99%

Multistate modeling and simulation for regulatory networks

Liu

Mobassera

Shaffer

et al. 2010

Proceedings of the 2010 Winter Simulation Conference

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Many protein regulatory models contain chemical species best represented as having multiple states. Such models stem from the potential for multiple levels of phosphorylation or from the formation of multiprotein complexes. We seek to support such models by augmenting an existing modeling and simulation system. Interactions between multistate species can lead to a combinatorial explosion in the potential state space. This creates a challenge when using Gillespie's stochastic simulation algorithm (SSA). Both the network-free algorithm (NFA) and various rules-based methods have been proposed to more efficiently simulate such models. We show how to further improve NFA to integrate population-based and particle-based features. We then present a population-based scheme for the stochastic simulation of rule-based models. A complexity analysis is presented comparing the proposed simulation methods. We present numerical experiments for two sample models that demonstrate the power of the proposed simulation methods.

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“…abundance initiates mitosis whereas starvation triggers meiosis (Barik et al, 2010;Kaizu et al, 2010;Nachman et al, 2007;Piekarska et al, 2010). Budding yeast cells can choose between meiosis or mitosis initiation alternatively according to the available nutrients until an irreversible point called 'commitment point' (Simchen, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…The available deterministic models can be categorised into two groups depending on their objectives: (1) cell cycle regulation focussed models, where the cell cycle is modelled and controlling mechanisms at checkpoints such as START, G1/S are studied by analysis (Barik et al, 2010;Tóth et al, 2007;Verdugo et al;Vinod et al, 2011); and (2) cell cycle's temporal organisation focussed models, which explain orderly progression of the cell cycle steps by the periodical activation and inactivation of the associated regulators (mainly Cdks and Cyclins) (Chen et al, 2004;Hong et al, 2012;Tyson and Novak, 2008).…”

Section: Introductionmentioning

confidence: 99%

A nutrient dependant switch explains mutually exclusive existence of meiosis and mitosis initiation in budding yeast

Wannige

Kulasiri

Samarasinghe

2014

Journal of Theoretical Biology

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Nutrients from living environment are vital for the survival and growth of any organism.Budding yeast diploid cells decide to grow by mitosis type cell division or decide to create unique, stress resistant spores by meiosis type cell division depending on the available nutrient conditions. To gain a molecular systems level understanding of the nutrient dependant switching between meiosis and mitosis initiation in diploid cells of budding yeast, we develop a theoretical model based on ordinary differential equations (ODEs) including the mitosis initiator and its relations to budding yeast meiosis initiation network. Our model accurately and qualitatively predicts the experimentally revealed temporal variations of related proteins under different nutrient conditions as well as the diverse mutant studies related to meiosis and mitosis initiation. Using this model, we show how the meiosis and mitosis initiators form an all-or-none type bistable switch in response to available nutrient level (mainly nitrogen). The transitions to and from meiosis or mitosis initiation states occur via saddle node bifurcation. This bidirectional switch helps the optimal usage of available nutrients and explains the mutually exclusive existence of meiosis and mitosis pathways.Key words: Bistable switching; Negative-feedback; Bifurcation; Saccharomyces cerevisiae Authors' contributions: The first and second authors developed the conceptual and mathematical models; the first author did all the computational work; the third author contributed to the data analysis, parameter estimation and clarifications related to the cell cycle; the first and second author wrote the paper with third author's assistance.

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A model of yeast cell‐cycle regulation based on multisite phosphorylation

Cited by 103 publications

References 74 publications

Mediator Phosphorylation Prevents Stress Response Transcription During Non-stress Conditions

Mediator Phosphorylation Prevents Stress Response Transcription During Non-stress Conditions

Multistate modeling and simulation for regulatory networks

A nutrient dependant switch explains mutually exclusive existence of meiosis and mitosis initiation in budding yeast

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