The G2 checkpoint - a node based molecular switch.mp4 (377.53 MB)
Dataset for: The G2 checkpoint: a node-based molecular switch
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posted on 2017-05-12, 10:28 authored by Mark Cornelis de Gooijer, Arnout van den Top, Irena Bockaj, Jos H Beijnen, Thomas Wurdinger, Olaf van TellingenTight regulation of the eukaryotic cell cycle is paramount to ensure genomic integrity throughout life. Cell cycle checkpoints are present in each phase of the cell cycle and prevent cell cycle progression when genomic integrity is compromised. The G2 checkpoint is an intricate signaling network that regulates the progression of G2 to mitosis (M). We propose here a node-based model of G2 checkpoint regulation, in which the action of the central CDK1–cyclin B1 node is determined by the concerted but opposing activities of the Wee1 and CDC25C nodes. Phosphorylation of both Wee1 and CDC25C at specific sites determines their subcellular localization, driving them either towards activity within the nucleus or to the cytoplasm and subsequent ubiquitin-mediated proteasomal degradation. In turn, this subcellular balance of the Wee1 and CDC25C nodes is directed by the action of the PLK1 and CHK1 nodes via what we have termed the ‘nuclear and cytoplasmic decision states’ of Wee1 and CDC25C. The proposed node-based model provides an intelligible structure of the complex interactions that govern the decision to delay or continue G2/M progression. The model may also aid in predicting the effects of agents that target these G2 checkpoint nodes.
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Categories
- Regenerative medicine (incl. stem cells)
- Synthetic biology
- Plant cell and molecular biology
- Animal cell and molecular biology
- Evolution of developmental systems
- Structural biology (incl. macromolecular modelling)
- Proteomics and intermolecular interactions (excl. medical proteomics)
- Evolutionary biology not elsewhere classified
- Signal transduction
- Cancer cell biology
- Systems biology
- Bioinformatics and computational biology not elsewhere classified
- Biostatistics
- Computational methods in fluid flow, heat and mass transfer (incl. computational fluid dynamics)
Keywords
G2 checkpointCDC25CCHK1PLK1cell cycleWee1Stem CellsSynthetic BiologyMolecular BiologyDevelopmental BiologyStructural BiologyProteomics and Intermolecular Interactions (excl. Medical Proteomics)Evolutionary BiologySignal TransductionCancer Cell BiologySystems BiologyBioinformaticsBiostatisticsHeat and Mass Transfer Operations
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