Entrainment of the Mammalian Cell Cycle by the Circadian Clock Modeling Two Coupled Cellular Rhythms 英文参考文献.docVIP

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Entrainment of the Mammalian Cell Cycle by the Circadian Clock Modeling Two Coupled Cellular Rhythms 英文参考文献.doc

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Entrainment of the Mammalian Cell Cycle by the Circadian Clock Modeling Two Coupled Cellular Rhythms 英文参考文献

EntrainmentoftheMammalianCellCyclebytheCircadian Clock:ModelingTwoCoupledCellularRhythms ClaudeGe′rard,AlbertGoldbeter* Faculte′ desSciences,Universite′ LibredeBruxelles(ULB),CampusPlaine,CP231,Brussels,Belgium Abstract The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupledinmultipleways,giventhatseveralmolecularcomponentsofthecellcyclenetworkarecontrolledinacircadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phasesofthecellcycle,thesynthesisofthekinaseWee1,whichinhibitstheG2/Mtransition,isenhancedbythecomplex CLOCK-BMAL1thatplaysacentralroleinthecircadianclocknetwork.Anothercomponentofthelatternetwork,REV-ERBa, inhibitsthesynthesisoftheCdkinhibitorp21.Moreover,thesynthesisoftheoncogenec-Myc,whichpromotesG1cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailedcomputational models for the two networks we investigate the conditionsinwhichthemammaliancellcyclecanbeentrainedbythecircadianclock.Weshowthatthecellcyclecanbe broughttooscillateataperiodof24hor48hwhenitsautonomousperiodpriortocouplingisinanappropriaterange. Themodelindicatesthatthecombinationofmultiplemodesofcouplingdoesnotnecessarilyfacilitateentrainmentofthe cellcyclebythecircadianclock.Entrainmentcanalsooccurasaresultofcircadianvariationsinthelevelofagrowthfactor controllingentryintoG1.Outsidetherangeofentrainment,thecouplingtothecircadianclockmayleadtodisconnected oscillationsinthecellcycleandthecircadiansystem,ortocomplexoscillatorydynamicsofthecellcycleintheformof endoreplication,complexperiodicoscillationsorchaos.Themodelpredictsthatthetransitionfromentrainmentto24hor 48hmightoccurwhenthestrengthofcouplingtothecircadianclockorthelevelofgrowthfactordecreasebelowcritical values. Citation:Ge′rard C,GoldbeterA(2012)EntrainmentoftheMammalianCellCyclebytheCircadianClock:ModelingTwoCoupledCellularRhythms.PLoSComput Biol8(5):e1002516.doi:10.1371/journal.pcb