学科分类
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53 个结果
  • 简介:TRAF2isacriticaladaptormoleculeforTNFreceptorsininflammatoryandimmunesignaling.Uponreceptorengagement,TRAF2isrecruitedtoCD40andtranslocatestolipidraftsinaRINGfinger-dependentprocess,whichenablestheactivationofdownstreamkinases.TRAF1candisplaceTRAF2andCD40fromraftfractions,anditpromotestheabilityofTRAF2tosustainsignalactivation.ReplacementoftheRINGfingerofTRAF2witharaft-targetingsignalrestoresJNKactivationandassociationwiththecytoskeletalproteinFilamin,butnotNF-KBactivation.TRAF1-/-dendriticcellsshowattenuatedresponses

  • 标签: TRAF2细胞内定位 TRAF1调节 信号转导机制
  • 简介:Bcl-2基因属于Bcl-2基因家族,其表达的Bcl-2蛋白在细胞凋亡过程中通过抑制线粒体中细胞色素C的释放,可明显地抑制细胞凋亡。由于在大规模的细胞培养过程中,细胞的死亡以凋亡为主,所以可通过建立稳定过表达Bcl-2蛋白的重组细胞株,以抑制细胞的凋亡。同时,Bcl-2蛋白的变化不但可预见肿瘤的发生,而且通过药物降低Bcl-2的含量对于肿瘤的治疗也具有积极的意义。本文综述了Bcl-2蛋白的结构、功能、抗凋亡作用的机理,以及目前在生物制药和临床方面的应用和前景。

  • 标签: BCL-2蛋白 代谢工程 抗癌药物
  • 简介:<正>Usingsubtractioncloning,weidentifiedthehumanN-MycDownstream-RegulatedGene-2(hNDRG2),locatedat14q11.2,asacandidatetumorsuppressorgene.Semi-quantitativeRT-PCRshowedthattheexpressionofhNDRG2in15of27(56%)humanGBMtissuesandall6humanglioblastomacelllineswassignificantlylowerthanthatinthenormalbrain.TheexpressionofhNDRG2alsowasevaluatedin60lung-carcinomapatients.17of26casesofsquamouscarcinomaand4of11casesofsmallcelllungcancerdisplayed

  • 标签: N-Myc减量调节基因2 NDRG2 细胞生长 负向调节 癌症 表达减少
  • 简介:GelatinaseA(MMP-2)isconsideredtoplayacriticalroleincellmigrationandinvasion.Theproteinaseiscercetedfromthecellasaninactivezymogen.InvivoitispostulatedthatactivationofprogelationaseA(proMMP-2)takesplaceonthecellsurfacemediatedbymembrane-typematrixmetalloproteinases(MT-MMPs).RecentstudieshavedemonstratedthatproMMP-2isrecruitedtothecellsurfacebyinteractingwithtissueinhibitorofmetalloproteinases-2(TIMP-2)boundtoMT1-MMPbyformingaternarycomplex.FreeMT1-MMPcloselylocatedtotheternarycomplexthenactivatesproMMP-2onthecellsurface.MT1-MMPisfoundinculturedinvasivecancercellsattheinvadopodia.TheMT-MMP/TIMP-2/MMP-2systemthusprovideslocalizedexpressionofproteolysisoftheextracellularmatrixrequiredforcellmigration.

  • 标签: 胞外基质 明胶酶原 细胞表面活化 细胞迁移
  • 简介:ErbB2,amemberofthereceptortyrosinekinasefamily,isfrequentlyover-expressedinbreastcancer.ProteolysisoftheextracellulardomainofErbB2resultsinconstitutiveactivationofErbB2kinase.RecentstudyreportedthatErbB2isfoundinthenucleus.Here,weshowedthatErbB2isimportedintothenucleusthroughanuclearlocalizationsignal(NLS)-mediatedmechanism.TheNLSsequenceKRRQQKIRKYTMRR(aa655-668)containsthreeclustersofbasicaminoacidsanditissufficienttotargetGFPintothenucleus.However,mutationinanybasicaminoacidclusterofthisNLSsequencesignificantlyaffectsitsnuclearlocalization.Furthermore,itwasfoundthatthisNLSisessentialforthenuclearlocalizationofErbB2sincetheintracellulardomainofErb2lackingNLScompletelyabrogatesitsnucleartranslocation.Takentogether,ourstudyidentifiedanovelnuclearlocalizationsignalandrevealsanovelmechanismunderlyingErbB2nucleartraffickingandlocalization.

  • 标签: 核子定位 信号转导 ErbB-2蛋白质 酪氨酸激酶 乳腺癌
  • 简介:在泰山虫草资源调查过程中,采集、分离获得一株泰山虫草菌(Cordycepssp.)。对其进行人工驯化栽培,发现其生长周期短,发菌快,适应性强。利用正交试验设计法筛选其最佳液体发酵培养基及条件,用SAS数据处理软件系统对菌丝生物量、多糖进行方差分析,并测定发酵液中超氧化物歧化酶(SOD)、过氧化物酶(POD)等酶的活性。结果表明,泰山虫草最优的菌丝体发酵培养基组合是:马铃薯20%、蔗糖2%、豆粉2%、胶体几丁质0.5%、无机盐0.1%KH2PO4、12h光照。

  • 标签: 泰山虫草 液体培养条件 正交试验
  • 简介:One-cellmouseembryosfromKMstrainandB6C3F1strainwereculturedinM16medium,inwhich2-cellblockgenerallyoccurs.EmbryosofKMstrainexhibited2-cellblock,whereasB6C3F1embryos,whichareregardedasanonblockingstrain,proceededtothe4-cellstageinourculturecondition.Itisoftenassumedthattheblockofearlydevelopmentisduetothefailureofzygoticgeneactivation(ZGA)inculturedembryos.Inthisstudyweexaminedproteinsynthesispatternsbytwo-dimensionalgelelectrophoresisof[35S]methionineradiolabeled2-cellembryos.Embryosfromtheblockingstrainandthenonblockingstrainwerecomparedintheirdevelopmentbothinvitroandinvivo.ThedetectionofTRCexpression,amarkerofZGA,at42hposthCGinKMembryosdevelopedinvitrosuggestedthatZGAwasalsoinitiatedeveninthe2-cellarrestedembryos.Nevertheless,asignificantdelayofZGAwasobservedinKMstrainascomparedwithnormallydevelopedB6C3F1embryos.AttheverybeginningofmajorZGAasearlyas36hposthCG,TRChasalreadybeenexpressedinB6C3F1embryosdevelopedinvitroandKMembryosdevelopedinvivo.Butfor2-cellblockedKMembryos,TRCwasstillnotdetectableevenat38hposthCG.Theseevidencessuggestthat2-cell-blockedembryosdoinitiateZGA,andthat2-cellblockphenomenonisduenottothedisabilityininitiatingZGA,buttoadelayofZGA.

  • 标签: 小鼠 两细胞胚胎 ZGA 阻抑
  • 简介:Humantumornecrosisfactorα(hTNFα),apleiotropiccytokinewithactivitiesrangingfromhostdefensemechanismsininfectionandinjurytoseveretoxicityinsepticshockorotherrelateddiseases,isapromisingtargetfordrugscreening.UsingtheSELEX(systematicevolutionofligandsbyexponentialenrichment)process,weisolatedoligonucleotideligands(aptamers)withhighaffinitiesforhTNFα.Aptamerswereselectedfromastartingpoolof40randomizedsequencescomposedofabout1015RNAmolecules.RepresentativeaptamersweretruncatedtotheminimallengthwithhighaffinityforhTNFαandwerefurthermodifiedbyreplacementof2'-OHwith2'-Fand2'-NH2atallribopurinepositions.ThesemodifiedRNAaptamerswereresistanttonuclease.ThespecificityoftheseaptamersforhTNFαwasconfirmed,andtheiractivitytoinhibitthecytotoxicityofhTNFαonmouseL929cellswasdetermined.Resultsdemonstratedthatfour2'-NH2-modifiedaptamersboundtohTNFαwithhighaffinityandblockedthebindingofhTNFαtoitsreceptor,thusprotectingtheL929cellsfromthecytotoxicityofhTNFα.OligonucleotideaptamersdescribedherearepotentialtherapeuticsanddiagnosticsforhTNFc-relateddiseases.

  • 标签: HTNFΑ 人肿瘤坏死因子Α 相似法则 RNA 核糖核酸 低聚核苷酸配位子
  • 简介:Domaindatabaseisessentialfordomainpropertyresearch.Eliminatingredundantinformationindatabasequeryisveryimportantfordatabasequality.Herewereportthemanualconstructionofanon-redundanthumanSH2domaindatabase.Thereare119humanSH2domainsin110SH2-containingproteins.HumanSH2swerealignedwithClustalX,andahomologoustreewasgenerated.Inthistree,proteinswithsimilarknownfunctionwereclassifiedintothesamegroup.Someproteinsinthesamegrouphavebeenreportedtohavesimilarbindingmotifsexperimentally.Thetreemightprovidecluesaboutpossiblefunctionsofhypotheticalproteinsforfurtherexperimentalverification.

  • 标签: 人类基因组计划 SH2域 同源性 系统进化树 非冗余数据库
  • 简介:Inordertostudythemechanismoftheeffectofheparinonapoptosisincarcinomacells,thenasopharyngealcarcinomacelllineCNE2wasusedtoidentifytheeffectofheparinonapoptosisassociatedwiththeexpressionofc-myc,bax,bcl-2proteinsbyuseofHoechst33258staining,terminaldeoxynucleotidyltransferase-mediateddUTPnick-endlabeling(TUNEL),agarosegelelectrophoresis,andflowcytometry,aswellasWesternblotanalysis.TheresultsshowedthatheparininducedapoptosisofCNE2cellsincludingthemorphologicchangessuchasreductioninthevolume,andthenuclearchromatincondensation,aswellasthe“ladderpattern”revealedbyagarosegelelectrophoresisofDNAinaconcentration-dependentmanner.ThenumberofTUNEL-positivecellswasdramaticallyincreasedto33.6±1.2%from2.8±0.3%bytreatmentwithheparinindifferentconcentrations(10~40kU/L).Theapoptoticindexwasincreasedto32.5%from3.5%bydetectingSubG1peaksonflowcytometry.Westernblotanalysisshowedthatlevelsofbcl-2,baxandc-mycweresignificantlyoverexpressedbytreatmentwiththeincreaseofheparinconcentrations.TheseresultssuggestthatheparininducesapoptosisofCNE2cells,whichmayberegulatedbydifferentialexpressionofapoptosis-relatedgenes.

  • 标签: 肝素 凋亡 咽鼓管癌 CNE2细胞
  • 简介:Apoptosismanifestsintwomajorexecutionprogramsdownstreamofthedeathsignal:thecaspasepathwayandorganelledysfunction.Animportantantiapoptosisfactor,Bcl-2protein,contributesincaspasepathwayofapoptosis.Calcium,animportantintracellularsignalelementincells,isalsoobservedtohavechangesduringapoptosis,whichmaybeaffectedbyBcl-2protein.WehavepreviouslyreportedthatinHarringtonine(HT)inducedapoptosisofHL-60cells,there'schangeofintracellularcalciumdistribution,ovingfromcytoplastespeciallyGolgi'sapparatustonucleusandaccumulatingtherewiththehighestconcentration.Wereportherethatcaspase-3becomesactivatedinHT-inducedapoptosisofHL-60cells,whichcanbeinhibitedbyoverexpressionofBcl-2protein.NosignofapoptosisorintracellularcalciummovementfromGolgi'sapparatustonucleusinHL-60cellsoverexpressingBcl-2ortreatedwithAc-DEVD-CHO,aspecificinhibitorofcaspase-3.Theresultsindicatethatactivatedcaspase-2canpromotethemovementofintracellularcalciumfromGolgi'sapparatustonucleus,andtheprocessisinhibitedbyAc-DEVD-CHO(inhibitorofcaspase-3),andthatBcl-2caninhibitthemovementandaccumulationofintracellularcalciuminnucleusthroughitsinhibitiononcaspase-3.Calciumrelocalizationinapoptosisseemstobeirreversible,whichisdifferentfromtheintracellularcalciumchangescausedbygrowthfactor.

  • 标签: HL-60细胞 细胞凋亡 Bol-2 Caspase-3 半胱氨酸天冬氨酸蛋白酶 胞内钙分布
  • 简介:竞争性寡聚脱氧核糖核酸识别转录因子的DNA结合域,抑制了转录因子对基因的转录调控,转录因子E2F作为潜在的治疗靶点,可以用于抑制肾小球系膜细胞和血管内皮细胞的增生,在部分异常增生的疾病中显示了一定的应用前景.

  • 标签: E2F 治疗靶点 细胞周期 DNA结合域 异常增生疾病
  • 简介:Threetypesofroughsurfacewereprocessedbylaserirradiationonthe3Cr2W8Vmaterialhot-workdiesteelsurface.Thewearexperimentswithsmoothsurfaceandroughsurfacesampleswererepeatedonthepin-traywearmachine.Accordingtothewearresults,westudiedtheregularityofwearresistanceofdifferentroughsurfacesamples.Theresultsindicatedthatbionicroughsurfacecanimprovethewearresistanceofthematerialandthewearresistancecanbeincreased1-2times,comparedwiththesmoothsurface.Also,thewearresistanceoftheroughsurfacewasaffectedbylasercurrentanddurationofimpulse.Thebiggerthelasercurrentortheimpulseduration,thebetteristhewearresistance.Whenthedistancebetweenthesamekindofunitswhicharedistributedonthesurfacesischanged,thewearresistancechanges.Thewearresistanceofabionicroughsurfaceonwhichthegridunitsweredistributedatspacingof1mmwasthebest.Andwedesignedthewearmodels.

  • 标签: 3CR2W8V 合金 粗糙表面 耐磨程度 仿生学
  • 简介:Polyamines在在植物,而是他们的准确角色调整各种各样的发展过程被含有并且他们怎么管理这些过程尚待逃犯。我们这里报导浓密的Arabidopsis和矮子异种,bud2,哪个从编码S-adenosylmethioninedecarboxylases(SAMDC)的小基因家庭的一个成员的完全的删除的结果为在polyamine简历的不可缺少的中介的形成必要合成小径。bud2植物在开花期,根,和叶柄扩大了脉管的系统,并且polyamines的改变的动态平衡。bud2和samdc1的双异种,另一个SAMDC成员的击倒的异种,是胚胎致命,证明SAMDC为植物胚胎开始是必要的。我们的结果建议polyamines为更高的植物的正常生长和发展被要求。

  • 标签: S-腺苷甲硫氨酸脱羧酶 基因编码 BUD2 植物构造
  • 简介:优良种质创新是大豆新品种选育的关键.经过近20年的中间种质创新、亲本筛选、抗性选育、鉴定和品质检验等研究,育成了双抗双高的夏大豆优良种质鲁99-2.其对大豆胞囊线虫1、3、5号生理小种的抗性均为1级;对大豆花叶病毒y6株系的抗性也为1级;籽粒脂肪含量平均为22.09%,高值为22.67%;蛋白质含量平均为43.29%,高值为45.0%;蛋白质和脂肪合计含量平均为65.38%,高值达66.40%.鲁99-2的育成说明创造和利用优良种质、选择适宜的杂交亲本和采用有效的选育方法等对大豆育种至关重要.

  • 标签: 夏大豆 种质 鲁99—2 选育 高脂肪 高蛋白质
  • 简介:利用构建的犬2型腺病毒E3区缺失质粒pBE3L分别构建了含有和不含外源性启动子的绿色荧光蛋白(GFP)基因和狂犬病病毒糖蛋白(Rgp)基因的重组表达质粒pBE3LGFP、pBE3LCGFP、pBE3LRgp和pBE3LCRgp,并分别对DK细胞进行了转染实验,以检测其表达,结果显示,pBE3LCGFP质粒在转染DK细胞后,于36h即可观察到荧光,72~96h无明显差别,传3代后仍可见表达荧光的细胞,pBE3LCRgp质粒转染DK细胞后,于48~96h用间接免疫荧光染色可检测到糖蛋白的表达,而pBE3LGFP和pBE3Rgp质粒转染DK细胞后经检测均无表达,表明构建的E3区缺失性载体不能利用E3区自身的启动子进行目的基因的表达,但利用外源性启动子可使外源基因获得良好表达.

  • 标签: 犬2型腺病毒 E3区 表达载体