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dc.contributor.author Lee, TJ
dc.contributor.author Yao, G
dc.contributor.author Bennett, DC
dc.contributor.author Nevins, JR
dc.contributor.author You, L
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:06Z
dc.date.issued 2010-09-21
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20877711
dc.identifier.citation PLoS Biol, 2010, 8 (9)
dc.identifier.uri http://hdl.handle.net/10161/4447
dc.description.abstract The transition of the mammalian cell from quiescence to proliferation is a highly variable process. Over the last four decades, two lines of apparently contradictory, phenomenological models have been proposed to account for such temporal variability. These include various forms of the transition probability (TP) model and the growth control (GC) model, which lack mechanistic details. The GC model was further proposed as an alternative explanation for the concept of the restriction point, which we recently demonstrated as being controlled by a bistable Rb-E2F switch. Here, through a combination of modeling and experiments, we show that these different lines of models in essence reflect different aspects of stochastic dynamics in cell cycle entry. In particular, we show that the variable activation of E2F can be described by stochastic activation of the bistable Rb-E2F switch, which in turn may account for the temporal variability in cell cycle entry. Moreover, we show that temporal dynamics of E2F activation can be recast into the frameworks of both the TP model and the GC model via parameter mapping. This mapping suggests that the two lines of phenomenological models can be reconciled through the stochastic dynamics of the Rb-E2F switch. It also suggests a potential utility of the TP or GC models in defining concise, quantitative phenotypes of cell physiology. This may have implications in classifying cell types or states.
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS Biol
dc.relation.isversionof 10.1371/journal.pbio.1000488
dc.subject Animals
dc.subject Blotting, Western
dc.subject Cell Cycle
dc.subject Cell Line
dc.subject E2F Transcription Factors
dc.subject Flow Cytometry
dc.subject Models, Biological
dc.subject Rats
dc.subject Stochastic Processes
dc.title Stochastic E2F activation and reconciliation of phenomenological cell-cycle models.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-9-0 en_US
duke.description.endpage e1000488 en_US
duke.description.issue 9 en_US
duke.description.startpage e1000488 en_US
duke.description.volume 8 en_US
dc.relation.journal Plos Biology en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20877711
pubs.issue 9
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Faculty
pubs.organisational-group /Duke/Pratt School of Engineering
pubs.organisational-group /Duke/Pratt School of Engineering/Biomedical Engineering
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.publication-status Published online
pubs.volume 8
dc.identifier.eissn 1545-7885

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