Beclin1调控自噬-凋亡与炎症反应的分子机制

aging〔M〕.CavanaughPress201217-21.40KlaskeWCobyAHansNetal.DesignofaＲandomisedControlledTrialＲCTontheeffectivenessofaDutchpatientadvocacycaseman-agementinterventionamongseverelydisabledmultiplesclerosispatients〔J〕．BMCHealthServＲes201010142.41KumamotoKArailYZaritSH.Useofhomecareserviceseffectivelyre-ducesfeelingsofburdenamongfamilycaregiversofdisabledelderlyinJapanpreliminaryresults〔J〕．IntJGeriatrPsychiatry2006221163-70.42WorldHealthOrganization.TheOttawaCharterforHealthPromotionEB/OL.1986-12-212010-03-29.http//ＲAngelJLetal.Variationinolderamericansactcaregiverserviceuseunmethoursofcareandindependenceamonghis-panicsAfricanAmericansandWhites〔J〕．HomeHealthCareServQ201332135-56.44CaasadoBLvanVulpenKSDavisSL.Unmetneedsforhomeandcom-munity-basedservicesamongfrailolderAmericansandtheircaregivers〔J〕．JAgingHealth2011233529-30.〔2013-07-30〕曲莉)Beclin1、郭鑫杨俊443003〔〕Beclin1〔〕Ｒ5〔〕A〔〕1005-9202201418-5289-03doi10.3969/j.issn.1005-9202.2014.18.14081170133812000881962-。1988-。。、、〔1〕。。DAMPs〔2〕。IL-1βIL-18。Bcl-2Beclin1。、Beclin1。1Becin1Beclin1BECN1Atg6/Vps30BethLevine1998。17q2112。Beclin160kD450BclBcl-2、Bcl-xl、Bcl-w。Beclin1BH3Bcl-2-homol-ogy-3、CCDECDN、CBeclin1。Beclin1“”。Vps34Ⅲ-3PIK3C3PI3PFYVE、。Beclin1Vps34。Vps34PKDproteinkinaseD〔3〕CDK5〔4〕Beclin1Vps34。2Beclin1-Vps34Beclin1-Vps34iAtg14Beclin1。AtgBeclin1、〔5〕ⅱUVＲAGBeclin1ⅲUVＲAG-ＲubiconＲubiconVps34。Atg14LUVＲAGBeclin1。Bif-1/B1UVＲAGVps34。-Ambra1Pink1Beclin1〔6〕。Beclin1Ambra1〔7〕Bim〔8〕Beclin1。ULK1Ambra1〔7〕JNKBim〔8〕Beclin1。3Beclin1、3.1Beclin1Beclin1·9825·Beclin1、18。Joubert〔9〕-CD46GOPCBeclin1Beclin1-Vps34。JoubertCD46/GOPC。Beclin1。UVＲAGC-VpsBeclin1-Vps34。Thoresn〔10〕Bclin1-Vps34-UVＲAG-Bif-1。Ｒuck〔11〕BEC1。Beclin1。Beclin1Beclin1〔12〕。Beclin1ULK1Beclin1-Vps34、。Grishchuk〔13〕Beclin1。Beclin1。Be-clin1。3.2Beclin13.2.1Beclin1Bcl-2Beclin1Bcl-2BH3-onlyBad、Bid、BNIP3、NoxaPuma。Bcl-2Bcl-2Bcl-xl、Bclw、Bcl-BMcl-1BH3Beclin1。Pattingre〔14〕Bcl-2Beclin-1Bcl-2Beclin1Beclin1-Vps34Vps34。Bcl-2/Beclin1Bcl-2/Beclin1。Bcl-2。3.2.2Beclin1Bcl-2Bcl-2Beclin1Bcl-2/Beclin1。Wei〔15〕JNK1Bcl-2。Bcl-2Thr69、Ser70Ser87Bcl-2Bec-lin1Beclin1Vps34。Pattingre〔16〕JNK1Bcl-2Beclin1。Sarkar〔17〕NOJNK1Bcl-2Bcl-2/Beclin1。DAPKBec-lin1BH3Thr119Beclin1/Bcl-2〔18〕。TLＲ4TＲAF6Beclin1K63Beclin1/Bcl-xL。3.2.3Beclin1Bcl-2Bcl-2Beclin1Bcl-2/Beclin1Beclin1。BH3-onlyBad、BidBNIP3、NoxaPumaBeclin-1Bcl-2/xLBH3。Bcl-2/xLBH3。AＲFBcl-xLBcl-xL/Beclin1〔19〕。3.3Beclin1。NLＲDAMPs。、Ⅱ。〔2〕。〔20〕Bcl-2Bcl-xLNLＲP1。Bcl-2NLＲP3〔21〕。Beclin1。NLＲC4、NLＲP3、NLＲP4NLＲP10Beclin1。NLＲP4Beclin1。NLＲP4NLＲC4。。Shi〔22〕THP-1AIM2NLＲP3。NLＲP3ASCLys63P62UBALC3。。4Beclin1HMGB1、TAB2/3。HMGB1。IL-1、TNFＲANKLTAB2TAB3TAK1。HMGB1、TAB2TAB3Beclin-1Bcl-2/Beclin-1。4.1Beclin1HMGB1Tang〔23〕HMGB1Beclin1Bcl-2/beclin1。HMGB1Beclin1Vps34/Vps15Beclin1。HMGB1HMGB1Beclin1。HMGB1Bcl-2/Beclin1EＲK1/2Bcl-2。〔24〕HMGB1p53。HMGB1p53p53HMGB1。HMGB1p53、。·0925·20149344.2Beclin1TAB2/3TAB2TAB3Bcl-2/Bec-lin1。TAB2TAB3Beclin1Beclin1。TAB2TAB3Beclin1Atg14L、UVＲAGAmbra1。5Beclin1。/Beclin1/〔25〕Beclin1/Bcl-2/。Beclin1、Beclin1。、、、Beclin1。61MizushimaNYoshimoriTOhsumiY.TheroleofAtgproteinsinautoph-agosomeformation〔J〕．AnnＲevCellDevBiol201127107-32.2SalminenAKaarnirantaKKauppinenA.Inflammagingdisturbedinter-playbetweenautophagyandinflammasomes〔J〕．AgingAlbanyNY20124166-75.3Eisenberg-LernerAKimchiA.PKDisakinaseofVps34thatmediatesＲOSinducedautophagydownstreamofDAPK〔J〕．CellDeathDiffer2012195788-97.4FuruyaTKimMLipinskiMetal.NegativeregulationofVps34byCdkmediatedphosphorylation〔J〕．MolCell2010384500-11.5ZhongYWangQJ.Atg14LandrubiconyinandyangofBeclin1-media-tedautophagycontrol〔J〕．Autophagy200956890-1.6VanHumbeeckCCornelissenTHofkensHetal.ParkininteractswithAmbra1toinducemitophagy〔J〕．JNeurosci2011312810249-61.7DiBartolomeoSCorazzariMNazioFetal.ThedynamicinteractionofAMBＲA1thedyneinmotorcomplexregulatesmammalianautophagy〔J〕．JCellBiol20101911155-68.8LuoSGarcia-ArencibiaMZhaoＲetal.Biminhibitsautophagybyre-cruitingbeclin1tomicrotubules〔J〕．MolCell2012473359-70.9JoubertPEMeiffrenGGregoireIPetal.AutophagyinductionbythepathogenreceptorCD46〔J〕．CellHostMicrob200964354-66.10ThoresenSBPedersenNMLiestolKetal.Aphosphatidylinositol3-ki-naseclassⅢsub-complexcontainingVPS15VPS34Beclin1UVＲAGandBIF-1regulatescytokinesisanddegradativeendocytictraffic〔J〕．ExpCellＲes2010316203368-78.11ＲuckAAttonitoJGarcesKTetal.TheAtg6/Vps30/Beclin1orthologBEC-1mediatesendocyticretrogradetransportinadditiontoautophagyinC.elegans〔J〕．Autophagy201174386-400.12CodognoPMehrpourMProikas-CezanneT.Canonicalandnon-canoni-calautophagyvariationsonacommonthemeofself-eating〔J〕NatureＲevMolCellBiol20121317-12.13GrishchukYGinetVTruttmannACetal.Beclin1-independentauto-phagycontributestoapoptosisincorticalneurons〔J〕．Autophagy20117101115-31.14PattingreSTassaAQuXetal.Bcl-2antiapoptoticproteinsinhibitBe-clin1-dependentautophagy〔J〕．Cell20051226927-39.15WeiYPattingreSSinhaSetal.JNK1-mediatedphosphorylationofBcl-2regulatesstarvation-inducedautophagy〔J〕．MolCell200830678-88.16PattingreSBauvyCCarpentierSetal.ＲoleofJNK1-dependentBcl-2phosphorylationinceramide-inducedmacroautophagy〔J〕．JBiolChem20