考研资料细胞生物学细胞增殖极其调控下课件

Contractilering:ActinandmyosinIIinthecontractileringgeneratetheforceforcytokinesis(2)Inplantcells:Thephragmoplastguidescytokinesisinhigherplants;Theassemblyofthecellplatebeginsinlateanaphaseandisguidedbyphragmoplast4.MeiosisThecomparisonofmeiosisandmitosisTwomajorcontributionstothereassortmentofgeneticmaterialthatoccursintheproductionofgametesduringmeiosis.VisibleevidenceofcrossingoverComparisonofthemechanismsofchromosomealignment(atmetaphase)andseparation(atanaphase)inmeioticdivisionIandmeioticdivisionII.MeioticchromosomepairingculminatesintheformationofthesynaptonemalcomplexInfluenceofSryongonaddevelopment.Thestagesofoogenesisandspermatogenesis

5.Thecell-cyclecontrolsystemA.Thecell-cyclecontrolsystemtriggersthemajorprocessesofthecellcycleB.ThecontrolsystemcanarrestthecellcycleatspecificcheckpointsC.Thecellcyclecontrolsystemisbasedoncyclicallyactivedproteinkinases---cyclin-dependentkinases(Cdks).Enginemoleculesforcellcycle

G1checkpoint:fissionyeastcells:Startpoint；Animalcells:RestrictionPointD.MPF(Maturation-promotingfactor，

Mitosis-promotingfactor)Lab.ofTorontoUnivandYaleUniv.maturationpromotingfactor,MPFPurdueUniv.:BehaviorofMPFThefusionofM-phaseHeLacellwithPtkcell(G1、S、G2)inducingPCC.Exp.Demonstrationthatcellscontainfactorsthatstimulateentryintomitosis.；Theprematurelycondensedchromosome(PCC)MPF(M-Cdk):p34cdc2cyclinB{Twosubunits:Catalyticsubunittransfers~PfromATPtoSerandThr;Regulatorysubunitcalledcyclin(MarineBiologicalLab.atWoodsHoleandUCBerkeleyUniv.ofOxford--yeast)E.Asimplifiedviewofthecoreofthecell-cycleconreolsystemCdkassociatessuccessivelywithdifferentcyclinstotriggerthedifferenteventsofthecycle.Cdkactivityisusuallyterminatedbycyclindegradation.Treeofcyclinsarerequiredinalleucaryoticcells:G1/S-cyclinsbindCdksattheendofG1andcommitthecelltoDNAreplication.S-cyclinsbindCdksduringSphaseandarerequiredfortheinitiationofDNAreplication.M-cyclinspromotetheeventsofmitosis.ThestructuralbasisofCdkactivationThehumanCdk2isshowninthreestates:(A)Intheinactive,withoutcyclinbound,theactivesiteisblockedbyaregionoftheproteincalledtheT-loop;(B)ThebindingofcyclincausestheT-looptomoveoutoftheactivesite,resultinginpartialactivitionofCdk2;(C)PhosphorylationofCdk2byCAKatathreonineresidueintheT-loop,fullyactive.Cdkactivitycanbesuppressedbothbyinhibitoryphosphorylation(pp586:14.6)andbyinhibitoryproteins(CKIs).P27—Cdkinhibitorproteins(CKIs)Thecell-cyclecontrolsystemdependsoncyclicalproteolysis---ThecontrolofproteolysisbySCFandAPCduringthecellcycle.(A)Thephosphorylationofatargetprotein(CKI),allowstheCKItoberecognizedbySCF(constitutiveactive),E1andE2(twoadditionalproteins),SCFservesasaubiquitinligase.TheubiquitylatedCKIisthenimmediatelyrecognizedanddegradedinaproteasome.SCFmediatethedestructionofG1-cyclins,Cdkinhibitor,andothercellcycleproteins.(B)M-cyclinubiquitylationisperformedbyAPC.InG1andSphaseInmetaphase/anaphaseM-cyclinsF.Intracellularcontrolofcell-cycleeventsS-phaseCyclin-Cdkcomplexes(S-Cdks)initiateDNAreplicationoncepercycleEvidencefromcell-fusionexp.Forareplicationblock.TheinitiationofDNAreplicationoncepercellcycle.ORC:originrecognitioncomplex;Cdc6:regulatoryprotein,itispresentatlowlevelsduringmostofthecellcyclebutincreasestransientlyinearlyG1,whereitisrequiredforthebindingofacomplexcomposedofagroupofcloselyrelatedproteins,theMcmproteins.TheactivationofM-phasecyclin-Cdkcomplexes(M-Cdks)triggersentryintomitosisTheactivationofM-CdkTheDNAreplicationcheckpoint:EntryintomitosisisblockedbyincompleteDNAreplication

TheexperimentsofDNAreplicationcheckpointinthemammaliancellsincultureweretreatedwithcaffeineandhydroxyurea.Thespindle-attachmentcheckpoint:Unattachedchromosomesblocksister-chromatidseparationThesisterchromatidseparationistriggeredbyproteolysisThetriggeringofsister-chromatidseparationbytheAPC.APC:anaphase-promotingcomplexThedestructionofSecurinallows

separasetocleavethecohesincomplex.Securin(后期抑制因子)separasecohesinMad2isnormallylocalizedatthekinetochoresofprometaphaseandmisalignedmetaphasechromosomes.Mad2providesa“wait”signalthatdelaysacell’sprogressionintoanaphase.ThecellthatpossessmutantMad2failtoarrestatmetaphasewhentheirchromosomesaremisaligned.Mad2bindtoCdc20,inhibitingitsactivationoftheAPC,aneventthatisrequiredforthemetaphase-to-anaphasetransition.ItisonlyaftertheMad2isabsentfromallofthechromosomesthatAPCactivationcanoccurandanaphasecanbegin.2.

ThecellthatcontainsMonoattachedchromosomedelaystheonsetofanaphaseuntilthechromosomebecomesabiattachedchromosomeandalignedattheequator.Mad2proteinonunattachedkinetochores.ExitfrommitosisrequirestheinactivationofM-CdkM-Cdkinactivationoccursmainlybyubiquitin-dependentproteolysisofM-cyclinsTheG1phaseisastateofstableCdkinactivityThecreationofaG1phasebystableCdkinhibitionaftermitosis.ThemechanismscotrollingS-phaseinitiationinanimalcells.TheRbproteinactsasabrakeinmammalianG1cellsThecontrolofG1progressionandS-phaseinitiationisoftendisruptedincancercells,leadingtounrestrainedcell-cycleentryandcellproliferation.MitogensstimulateG1-CdkandG1/S-CdkactivitiesAsimplifiedmodelofonewaythatmitogensstimulatecelldivisionDNAdamagecheckpoint:

Cell-cycleprogressionisblockedbyDNAdamageand

p53HowDNAdamagearreststhecellcycleinG1.Twosuchcheckpoints:1.OneinlateG1:proventsentryintoSphase;2.OneinlateG2:proventsentryintomitosis;P53:generegulatoryprotein.DNAdamageactivatesp53byanindirectmechanism.Mdm2actsasaubiquitinligasethattargetsp53fordestructionbyproteasomes.Phosphrylatedp53reduceitsbindingtoMdm2.P21(CKIprotein)bindstoG1/S-CdkandS-Cdkandinhibitstheiractivities,therebyhelpingtoblockentryintoSphase.Thesummaryofcell-cyclecontrolsystemSummaryAnorderedsequenceofcyclin-Cdkactivitiestriggersmostoftheeventsofthecellcycle.DuringG1phase,CdkactivityisreducedtoaminimumbyCdkinhibitors(CKIs),cyclinproteolysis,anddecreasedcyclingenetranscription.Whenenvironmentalconditionsarefavorable,G1-andG1/S-Cdksincreaseinconcentration,overcomingtheseinhibitorybarriersinlateG1andtriggeringtheactivationofS-Cdk.TheS-CdkphosphorylatesproteinsatDNAreplicationorigins,initiatingDNAsynthesi