Abstract:
:Tight 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 cell division control protein 25C (CDC25C) nodes. Phosphorylation of both Wee1 and CDC25C at specific sites determines their subcellular localization, driving them either toward 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.
journal_name
FEBS Open Biojournal_title
FEBS open bioauthors
de Gooijer MC,van den Top A,Bockaj I,Beijnen JH,Würdinger T,van Tellingen Odoi
10.1002/2211-5463.12206subject
Has Abstractpub_date
2017-03-04 00:00:00pages
439-455issue
4issn
2211-5463pii
FEB412206journal_volume
7pub_type
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