Dataset Information

DeBoeck2021 - Modular approach to modeling the cell cycle, simple cell cycle model

ABSTRACT: Models the production and degradation of cyclin B that drives the early embryonic cell cycle. Cyclin B is degraded by APC/C. The activity of APC/C is modeled not through biochemical interactions, but through a 'functional response curve'. This can be ultrasensitive (with the parameter alpha=0). in this case the system does not oscillate. Importantly the response can be made bistable and the form of the bistability can be easily prescribed. With a bistable response, the system oscillates. The uploaded file corresponds to the model used for Figs.3H, I in the publication.

SUBMITTER: Jan Rombouts

PROVIDER: BIOMD0000001079 | BioModels | 2024-01-29

REPOSITORIES: BioModels

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Publications

A modular approach for modeling the cell cycle based on functional response curves.

De Boeck Jolan J Rombouts Jan J Gelens Lendert L

PLoS computational biology 20210811 8

Modeling biochemical reactions by means of differential equations often results in systems with a large number of variables and parameters. As this might complicate the interpretation and generalization of the obtained results, it is often desirable to reduce the complexity of the model. One way to accomplish this is by replacing the detailed reaction mechanisms of certain modules in the model by a mathematical expression that qualitatively describes the dynamical behavior of these modules. Such ...[more]

PMID: 34379640

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Project description:In the budding yeast Saccharomyces cerevisiae, transcription factors (TFs) regulate the periodic expression of many genes during the cell cycle, including gene products required for progression through cell-cycle events. Experimental evidence coupled with quantitative models suggest that a network of interconnected TFs is capable of regulating periodic genes over the cell cycle. Importantly, these dynamical models were built on transcriptomics data and assumed that TF protein levels and activity are directly correlated with mRNA abundance. To ask whether TF transcripts match protein expression levels as cells progress through the cell cycle, we applied a multiplexed targeted mass spectrometry approach (parallel reaction monitoring) on synchronized populations of cells. We found that protein expression of many TFs and cell-cycle regulators closely followed their respective mRNA transcript dynamics in cycling wild-type cells. Discordant mRNA/protein expression dynamics were also observed for a subset of cell-cycle TFs and for proteins targeted for degradation by E3 ubiquitin ligase complexes such as SCF (Skp1/Cul1/F-box) and APC/C (anaphase-promoting complex/cyclosome). We further profiled mutant cells lacking B-type cyclin/CDK activity (clb1-6), where oscillations in ubiquitin ligase activity, cyclin/CDKs, and cell-cycle progression are halted. We found that a number of proteins were no longer periodically degraded in clb1-6 mutants compared to wild type, highlighting the importance of post-transcriptional regulation. Finally, the TF complexes responsible for activating G1/S transcription (SBF and MBF) were more constitutively expressed at the protein level than their periodic mRNA expression levels in both wild-type and mutant cells. This comprehensive investigation of cell-cycle regulators reveals that multiple layers of regulation (transcription, protein stability, and proteasome targeting) affect protein expression dynamics during the cell cycle.

Dataset Information

DeBoeck2021 - Modular approach to modeling the cell cycle, simple cell cycle model

Publications

A modular approach for modeling the cell cycle based on functional response curves.

Similar Datasets

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