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1、Progressintheeukaryoticcellcycleisdrivenbyoscillations(振动)intheactivitiesofCDKs(Cyclin-DependentKinases).CDKactivityiscontrolledbyperiodicsynthesis（周期复合体）anddegradationofpositiveregulatorysubunits（调节亚基）,Cyclins,aswellasbyfluctuationsinlevelsofnegativeregulators,byCKIs(CDKInhibitor
2、s),andbyreversiblephosphorylation.Themammaliancellcycleconsistsoffourdiscretephases:S-phase,inwhichDNAisreplicated;M-phase,inwhichthechromosomesareseparatedovertwonewnucleiintheprocessofmitosis.Thesetwophasesareseparatedbytwosocalled“Gap”phases,G1andG2,inwhichthecellpreparesforthe
3、upcomingeventsofSandM,respectively(Ref.1).ThedifferentCyclins,specificfortheG1-,S-,orM-phasesofthecellcycle,accumulateandactivateCDKsattheappropriatetimesduringthecellcycleandthenaredegraded,causingkinaseinactivation.LevelsofsomeCKIs,whichspecificallyinhibitcertainCyclin/CDKcomple
4、xes,alsoriseandfallatspecifictimesduringthecellcycle(Ref.2).Abreakdownintheregulationofthiscycleleadstouncontrolledgrowthandcontributetotumorformation.Defectsinmanyofthemoleculesthatregulatethecellcyclealsoleadtotumorprogression.Keyamongthesearep53,theCKIs(p15(INK4B),p16(INK4A),p1
5、8(INK4C),p19(INK4D),p21,p27(KIP1)),andRb(RetinoblastomaSusceptibilityProtein),allofwhichacttokeepthecellcyclefromprogressinguntilallrepairstodamagedDNAhavebeencompleted.Inmammaliancells,differentCyclin-CDKcomplexesareinvolvedinregulatingdifferentcellcycletransitions:Cyclin-D-CDK4/
6、6forG1progression,Cyclin-E-CDK2fortheG1-Stransition,Cyclin-A-CDK2forS-phaseprogression,andCyclin-A/B-CDC2forentryintoM-phase.Apartfromthesewell-knownrolesinthecellcycle,severalCyclinsandCDKsareinvolvedinprocessesnotdirectlyrelatedtothecellcycle.Cyclin-Dbindsandactivatestheestrogen
7、receptor.(Ref.6).TheCyclin-H-CDK7complexisacomponentofboththeCDK-activatingkinaseandthebasaltranscriptionfactorTFIIHandcanphosphorylateCDKs.OtherCyclinsandCDKs(Cyclin-C-CDK8,Cyclin-T-CDK9,andCyclin-K)arealsoassociatedwithRNAPolymerase-IIandphosphorylatethecarboxyl-terminalrepeatdo
8、main.Cyclin-G,atargetofp53,recrui
