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隆天知识产权
Thechromatinpackagingofthegenomeisdynamic,changingwiththecellcycleandwithtranscriptionalregulation.Duringmitosis,chromatiniscondensedforsegregationofchromosomes,whilefortranscriptionchromatinismoreopen.Thenuclearmatrix,orscaffold,isaproteinnetworkinthenucleusprovidingstructureandregulatingchromatincondensation.Regulatedinteractionsofmatrixproteinswitheachother,DNAandotherfactorsindifferentphasesofthecellcyclealterthestructureandfunctionofchromatin.AKAP95(A-kinaseanchoringprotein)isanuclearmatrixassociatedproteinthatalsobindsDNAanddifferentproteinsduringdifferentphasesofthecellcycle.TheinteractionofAKAP95withDNAandproteinsaltersthecondensationandtranscriptionofchromatin.AspecificdomainofAKAP95regulatesitsinteractionwiththenuclearmatrixandanotherregulatesitsassociationwithDNA.OnekeyproteinthatAKAP95interactswithisthecAMP-dependentproteinkinase,PKA.AKAP95bindstoPKAthroughaPKARIIregulatorysubunit,aninteractionthatrequiresPKAphosphorylationbyCdk1.PKAactivityandcAMParereducedduringentryintomitosis,butPKArecruitedbyAKAP95tocondensedchromosomesisessentialtomaintainthecondensedstate.AnotherproteinrecruitedbyAKAP95isEg7,a150kDproteinrecruitedduringmitoticchromatincondensation.Eg7isapartofamultiproteincondensincomplex,recruitinganotherkeycomponentofmitoticchromatincondensation.Modificationofthecorehistonesthroughphosphorylationregulateschromatincondensation.HistoneH3interactswiththecondensincomplex,andisphosphorylatedduringmitosis.HistoneH3phosphorylationbyAurora-2induceschromatincondensation,anddephosphorylationbyPP1promoteschromatindecondensationforreentryintointerphase.AKAP95mayplayaroleduringtheregulationofchromatinstructurefortranscriptionduringinterphaseaswell.TheinteractionofAKAP95withthep68RNAhelicaserecruitsthisenzymetothenuclearmatrixduringinterphase.OthernuclearRNAhelicasesinteractwithtranscriptionfactorsandcofactors,suggestingthatthep68RNAhelicasealsomayregulateinteractionsoftranscriptioncomplexes. Contributor:KosiGramatikoff REFERENCES:AkileswaranL,TaraskaJW,SayerJA,GettemyJM,CoghlanVM.A-kinase-anchoringproteinAKAP95istargetedtothenuclearmatrixandassociateswithp68RNAhelicase.JBiolChem.2001May18;276(20):17448-54.BallARJr,SchmiesingJA,ZhouC,GregsonHC,OkadaY,DoiT,YokomoriK.Identificationofachromosome-targetingdomaininthehumancondensinsubunitCNAP1/hCAP-D2/Eg7.MolCellBiol.2002Aug;22(16):5769-81.CollasP,LeGuellecK,TaskenK.TheA-kinase-anchoringproteinAKAP95isamultivalentproteinwithakeyroleinchromatincondensationatmitosis.JCellBiol.1999Dec13;147(6):1167-80.EideT,CarlsonC,TaskenKA,HiranoT,TaskenK,CollasP.DistinctbutoverlappingdomainsofAKAP95areimplicatedinchromosomecondensationandcondensintargeting.EMBORep.2002May;3(5):426-32.LandsverkHB,CarlsonCR,SteenRL,VossebeinL,HerbergFW,TaskenK,CollasP.RegulationofanchoringoftheRIIalpharegulatorysubunitofPKAtoAKAP95bythreoninephosphorylationofRIIalpha:implicationsforchromosomedynamicsatmitosis.JCellSci.2001Sep;114(Pt18):3255-64.MurnionME,AdamsRR,CallisterDM,AllisCD,EarnshawWC,SwedlowJR.Chromatin-associatedproteinphosphatase1regulatesaurora-BandhistoneH3phosphorylation.JBiolChem.2001Jul13;276(28):26656-65.SchmiesingJA,GregsonHC,ZhouS,YokomoriK.AhumancondensincomplexcontaininghCAP-C-hCAP-EandCNAP1,ahomologofXenopusXCAP-D2,colocalizeswithphosphorylatedhistoneH3duringtheearlystageofmitoticchromosomecondensation.MolCellBiol.2000Sep;20(18):6996-7006.SteenRL,CubizollesF,LeGuellecK,CollasP.Akinase-anchoringprotein(AKAP)95recruitshumanchromosome-associatedprotein(hCAP)-D2/Eg7forchromosomecondensationinmitoticextract.JCellBiol.2000May1;149(3):531-6.
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