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1、Chapter13CellapoptosisExtracellularcotrolofcelldivision,cellgrowth,andapoptosisMitogensstimulateG1-CdkandG1/S-CdkactivitiesPRIZEDHorvitz,andSulstonsharePhysiologyorMedicineNobel(2002)“fortheirdiscoveriesconcerninggeneticregulationoforgandevelopmentandprogrammedcellde
2、ath”1090–131=959(cells)機(jī)體結(jié)構(gòu)細(xì)胞增殖細(xì)胞分化細(xì)胞凋亡細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)染色體(DNA與蛋白質(zhì)的相互作用)衰老?AsimplifiedmodelofonewaythatmitogensstimulatecelldivisionHumancellshaveabuilt-inlimitationonthenumberoftimestheycandivideThecelldivisioniscotrollednotonlybyextracellularmitogensbutalsobyintracellularmec
3、hanismsthatcanlimitcellproliferation.Cell-cyclearrestorapoptosisinducedbyexcessivestimulationofmitogenicpathways.ExtracellulargrowthfactorsstimulatecellgrowthActivationofcell-surfacereceptorsActivationofPI3-kinaseActivationofelF4E(translationinitiationfactor)andS6kin
4、ase(phosphorylatesribosomalproteinS6)Increasingproteinsynthesisandcellgrowth2.Apoptosis,ProgrammedcelldeathBiologicalfunctionsofapoptosis?Indevelopment,homeostasis,tumorsurveillance,andthefunctionoftheimmunesystem.?細(xì)胞凋亡是多細(xì)胞生物在發(fā)育過程中,一種由基因控制的主動(dòng)的細(xì)胞生理性自殺行為。Morphologicala
5、ndbiochemicalcharacteristicsofapoptosis?Morphologichanges:Early:Chromosomecondensation,cellbodyshrinkLater:BlebbingandNucleusandcytoplasmfragment—ApoptoticbodiesAtlast:PhagocytosedA、NormalcellB、Apoptosis:Apoptoticbodies?Biochemicalcharacteristicsofapoptosis:Apoptosis
6、inducedbyCytoCLane1.0h2.1h3.2h4.3h5.4h6.Control7.Marker2.0kbp1.00.50.2180~200bpDNAladder,AccumulationoftTG,PSflip-flopContrastofApoptosisandnecrosisApoptosisNecrosisDeathbyapoptosisisaneat,orderlyprocess3.MolecularmechanismsofapoptosisEarlyresearches(MIT:RobertHorrid
7、,1986)C.elegans:1090cells,TheFindingofCED3mutantWithoutlosinganyoftheircellstoapoptosis.CED3geneplayacrucialroleintheprocessofapoptosis.Celegans:amillimeterlong,transparentbodyonlyafewcelltypes,fromzygotetomatureadultonlyin3.5days.131cellsdeath.線蟲體細(xì)胞凋亡研究:PCD相關(guān)基因15個(gè),分
8、為四組:1、與PCD有關(guān)的基因,負(fù)責(zé)PCD控制:ced-3、ced-4和ced-9。2、與PCD過程吞噬作用有關(guān):ced-1、ced-2、ced-5-8和ced-10。3、核酸酶基因(nuc-1),控制DNA降解,但非PCD所必須。4、影響特異細(xì)胞類型PCD的基