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1、Chapter13CellapoptosisExtracellularcotrolofcelldivision,cellgrowth,andapoptosisMitogensstimulateG1-CdkandG1/S-CdkactivitiesPRIZEDHorvitz,andSulstonsharePhysiologyorMedicineNobel（2002）“fortheirdiscoveriesconcerninggeneticregulationoforgandevelopmentandprogrammedcellde
2、ath”1090–131=959(cells)機體結(jié)構(gòu)細胞增殖細胞分化細胞凋亡細胞信號轉(zhuǎn)導染色體（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.?細胞凋亡是多細胞生物在發(fā)育過程中，一種由基因控制的主動的細胞生理性自殺行為。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.線蟲體細胞凋亡研究：PCD相關基因15個，分
8、為四組：1、與PCD有關的基因，負責PCD控制：ced-3、ced-4和ced-9。2、與PCD過程吞噬作用有關：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、影響特異細胞類型PCD的基
