简介：

简介：

简介：Uponencounteringtheantigen(Ag),theimmunesystemcaneitherdevelopaspecificimmuneresponseofenteraspecificstateofunresponsiveness,tolerance.TheresponseofBcellstotheirspecificAgcanbeactivationandproliferation,leadingtotheimmuneresponse,oranergyandactivation-inducedcelldeath(AICD),leadingtotolerance.AICDinBlymphocytesisahighlyregulatedeventinitiatedbycrosslinkingoftheBcellreceptor(BCR).BCRengagementinitiatesseveralsignalingeventssuchasactivationofPLCγ,Ras,andPI3K,whichgenerallyspeaking,leadtosurvival.However,intheabsenceofsurvivalsignals(CD40orIL-4Rengagement),BCRcrosslinkingcanalsopromoteapoptoticsignaltransductionpathwayssuchasactivationofeffectorcaspases,expressionofpro-apoptoticgenes,andinhibitionofpro-survivalgenes.ThecomplexinterplaybetweensurvivalanddeathsignalsdeterminestheBcellfateand,consequently,theimmuneresponse.

简介：LRP16以前在乳癌房间作为导致雌激素的基因被识别。到在子宫内膜的癌症(EC)的雌激素和它的功能的效果的LRP16的应答的海角房间仍然是不清楚的。这里，我们证明LRP16基因的信使rna水平和倡导者活动被17beta-estradiol(E2)显著地在雌激素受体高山增加哈(嗯高山哈)-positiveIshikawa人EC房间。尽管Ishikawa细胞的生长率没被LRP16的宫外的表示显然影响，Transwell试金的结果显示出LRP16-overexpressing细胞的侵略能力的近似one-thirdincrease。由于分子的屏蔽，我们观察到E-cadherin的表示，与肿瘤转移联系的一个必要粘附分子，被LRP16镇压。进一步的倡导者分析以一种剂量依赖者方式表明了那LRP16inhibitedE-cadherintransactivation。然而，抑制被雌激素剥夺废除，显示由LRP16requires的E-cadherin抄写的down规定嗯高山哈调停。染色质免疫降水分析表明到E-cadherin倡导者的ERalpha的绑定被LRP16反对，建议那LRP16能防碍嗯调停alpha的抄写。这些结果建议起来由雌激素的LRP16的规定能被在人的EC调整E-cadherin的down涉及侵略生长。

简介：ApoptosisproducedinBcellsthroughFas(APO-1,CD95)triggeringisregulatedbysignalsderivedfromothersurfacereceptors:CD40engagementproducesupregulationofFasexpressionandmarkedsusceptibilitytoFas-inducedcelldeath,whereasantigenreceptorengagement,orIL-4Rengagement,inhibitsFaskillingandinsodoinginducesastateofFas-resistance,eveninotherwisesensitive,CD40-stimulatedtargets.SurfaceimmunoglobulinandIL-4RutilizeatleastpartiallydistinctpathwaystoproduceFas-resistancethatdifferentiallydependonPKCandSTAT6,respectively.Further,surfaceimmunoglobulinsignalingforinducibleFas-resistancebypassesBtk,requiresNF-κB,andentailsnewmacromolecularsynthesis.TerminaleffectorsofBcellFas-resistanceincludetheknownanti-apoptoticgeneproducts,Bcl-XLandFLIP,andanovelanti-apoptoticgenethatencodesFAIM(FasApoptosisInhibitoryMolecule).faimwasidentifiedbydifferentialdisplayandexistsintwoalternativelysplicedforms;faim-Sisbroadlyexpressed,butfaim-Lexpressionistissue-specific.TheFAIMsequenceishighlyevolutionarilyconserved,suggestinganimportantroleforthismoleculethroughoutphylogeny.InducibleresistancetoFaskillingishypothesizedtoprotectforeignantigen-specificBcellsduringpotentiallyhazardousinteractionswithFasL-bearingTcells,whereasautoreactiveBcellsfailtobecomeFas-resistantandaredeletedviaFas-dependentcytotoxicity.InadvertentoraberrantacquisitionofFas-resistancemaypermitautoreactiveBcellstoescapeFasdeletion,andmalignantlymphocytestoimpedeanti-tumorimmunity.

简介：<正>ThesusceptibilityofprimaryBcellstoFas(APO-1,CD95)-mediatedapoptosisisregulatedbysignalsderivedfromadditionalsurfacereceptors.CD40engagementproducesupregulationofFasexpressionandinducesmarkedsensitivitytoFas-inducedcelldeath,whereasBcellantigenreceptor(BCR)engagementinhibitsFaskillingandtherebyproducesFas-resistance,eveninotherwisesusceptible,CD40-stimulatedtargets.BCRsignalingforinducibleFas-resistancedevelopsoveraperiodof12hoursanddependson

简介：被象染色体冷凝作用，面向双性人的锭子形成，染色体大会离子，分离和胞质分裂那样的一系列紧安排的事件精确通过有丝分裂调整。染色体运动被和位于着丝点以内的一个专业化染色体领域的锭子微导管的相互作用在有丝分裂期间管理。这个专业化区域，叫了kinetochore，是为锭子微导管着丝点的地点协会。除了用作在染色体和锭子微导管之间的一个物理连接，kinetochore通过微导管马达和定位在或在它附近的锭子集会检查点(囊)传感器在chromosomal分离展出一个活跃角色[例如，1]。

简介：<正>Uponactivation,naiveT-helpercellscandifferentiateintotwomajordistinctsubsets,Thelper1(Th1)andThelper2(Th2),asdefinedbytheireffectorfunctionsandcytokinesecretionpatterns.CytokinemilieuandcostimulatorymoleculeshavebeenshowntoplayanessentialroleindeterminingThelperdifferentiation.However,itisstillunclearhowtheeffectsofsignalsofco-stimulatorymoleculesandcytokinesareexertedduringThelperdifferentiation.Weshowevidencesuggestingthatwhilecytokinesignalsinitiatedifferentiationprogram,theselectiveactionofdeatheffectorsdeterminestheendpointbalanceofdifferenti-

简介：<正>WeandothershavefirmlyestablishedthatsurfaceIgMreceptor(sIgM-R)crosslinkingwithantibodiestotheiheavychain(anti-i)leadstogrowtharrestandapoptosisinaseriesofwellcharacterizedB-celllymphomas.Thisrequiresablationofc-Mycproteinexpressionandtheconcomitantinductionofthecyclin-dependent-kinaseinhibitor,p27Kip1.Thesignalingmechanismsregulatingc-Mycandp27Kip1proteinexpressionarepoorlyunderstood.However,werecentlyestablishedthatsIgM-Rmediateddown-modulationofthePI-3Kpathwaydirectlyaffectedc-Mycandp27Kip1expressionandaccuratelypredictedgrowtharrest

简介：

简介：记忆B和T淋巴细胞的功能的角色位于预防种痘的非凡的成功下面，它减少了从传染疾病的病态和死亡全球性在最后50年。然而，逐渐地欣赏了那，正在变得记忆房间也能够调停与自体免疫的混乱联系的病理并且移植拒绝，并且可以提出一个重要障碍到未来在immunoregulation的临床的前进。因此，理解记忆淋巴细胞的唯一的性质(作为与他们的天真的先锋相比)是调查的一个主要区域。这里，我们集中于记忆T房间(TM)的那些单个性质之一鈥攔apid召回。当愿望更详细地被讨论，快速的召回指静止TM房间的能力到“高效地并且要用体力地快速的受动器功能”跟随刺激。用CD4+T房间推进了我们TM房间的快速的召回的理解的研究是熟练地在其它地方考察了1，我们将因此首先集中于CD8+T房间的研究。我们将首先考察CD8+TM房间能被产生的不同方法，由讨论这怎么在有免疫力的保护和病理的背景影响他们的功能的性质列在后面。然后，快速的召回能力将被讨论，与放在当前对机制被知道位于TM房间的这个唯一的性质下面的上的强调。

简介：Thenon-classicalHLAclassIantigenHLA-GisanimmunemodulatorwhichinhibitsthefunctionsofTcells,NKcells,andtheDendriticcells(DC).Asaresult,HLA-Gexpressioninmalignantcellsmayprovidethemwithamechanismtoescapetheimmunesurveillance.Inmelanoma,HLA-Gantigenexpressionhasbeenfoundin30%ofsurgicallyremovedlesionsbutinlessthan1%ofestablishedcelllines.OnepossiblemechanismunderlyingthedifferentialHLAGexpressioninvivoandinvitroisthattheHLA-Ggeneisepigeneticallyrepressedinmelanomacellsinvitro.Totestthishypothesis,wetreatedtheHLA-GnegativemelanomacelllineOCM-1AwiththeDNAmethyltransferaseinhibitor5-aza-2'-deoxycytidine(5-AC)andanalyzedwhetherHLA-Gexpressioncanberestored.OurdatastronglysuggestthatHLA-GissilencedasaresultofCpGhypermethylationwithina5'regulatoryregionencompassing220bpupstreamofthestartcodon.Aftertreatment,HLA-GmRNAexpressionwasdramaticallyincreased.WesternblotandflowcytometryshowedthatHLA-Gproteinwasinduced.Interestingly,HLA-Gcellsurfaceexpressiononthe5-ACtreatedOCM-1AcellsismuchlessthanthatontheHLA-GpositiveJEG-3cellswhileasimilaramountoftotalHLA-Gwasobserved.Possiblemechanismsforthedifferencewereanalyzedinthestudysuchascellcold-treatment,peptideloadingandantigenprocessingmachinerycomponents(APM)aswellasβ2microglobulin(β2-m)expression.DatarevealedthattheAPMcomponentcalreticulinmightbeinvolvedinthelowerHLA-GsurfaceexpressiononOCM-1Acells.Takentogether,ourresultsindicatedthatDNAmethylationisanimportantepigeneticmechanismbywhichHLA-Gantigenexpressionismodulatedinmelanomacellsinvitro.Furthermore,tothefirsttime,wehypothesizedthatthedeficiencyofcalreticulinmightbeinvolvedinthelowHLA-Gsurfaceexpressiononthe5-ACtreatedOCM-lAcells.

简介：TRAF2isacriticaladaptormoleculeforTNFreceptorsininflammatoryandimmunesignaling.Uponreceptorengagement,TRAF2isrecruitedtoCD40andtranslocatestolipidraftsinaRINGfinger-dependentprocess,whichenablestheactivationofdownstreamkinases.TRAF1candisplaceTRAF2andCD40fromraftfractions,anditpromotestheabilityofTRAF2tosustainsignalactivation.ReplacementoftheRINGfingerofTRAF2witharaft-targetingsignalrestoresJNKactivationandassociationwiththecytoskeletalproteinFilamin,butnotNF-KBactivation.TRAF1-/-dendriticcellsshowattenuatedresponses

简介：

简介：与一级的CD8约会主要组织亲和性抗原极大地提高T房间激活，但是这怎么被完成，不是清楚的。我们探讨CD8的调停抗体的结扎是否独自导致在T房间克隆改变的transcriptional的问题，用基因表示的连续分析。尽管它没能导致公开phenotypic变化，我们发现CD8结扎深刻地在T房间克隆改变抄写，在比得上由CD3的调停抗体的结扎导致了那的规模。然而，产生变化的特性与是实质地禁止的CD8结扎的网效果是不同的。我们推测那绑扎的CD8导致弱，T房间受体(TCR)调停了TCR对手的效果暗示的禁止的信号。我们的结果暗示CD8结扎独自不能因为它没能充分导致NFAT依赖的抄写，激活T房间克隆。

简介：<正>Usingsubtractioncloning,weidentifiedthehumanN-MycDownstream-RegulatedGene-2(hNDRG2),locatedat14q11.2,asacandidatetumorsuppressorgene.Semi-quantitativeRT-PCRshowedthattheexpressionofhNDRG2in15of27(56%)humanGBMtissuesandall6humanglioblastomacelllineswassignificantlylowerthanthatinthenormalbrain.TheexpressionofhNDRG2alsowasevaluatedin60lung-carcinomapatients.17of26casesofsquamouscarcinomaand4of11casesofsmallcelllungcancerdisplayed

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.

简介：在哺乳动物的胚胎，内部房间团(ICM)的分离和trophectoderm(TE)的第一种房间命运选择，，被抄写因素，Oct4和Cdx2的互相对抗的效果调整pluripotency因素，Nanog，是必要的指定epiblast。我们分析了Nanog和Cdx2的倡导者，并且发现了这二个抄写因素同样相互地被调整。用有有条件的TE区别的一根胚胎的干细胞线，我们证明Nanogoverexpression压制TE标记的upregulation，当时Nanog击倒的upregulatesTE标记的表示。我们推进Nanog和Cdx2绑在并且镇压的表演对方的倡导者。而Nanog大美人在ICM导致可检测的Cdx2表示，我们不管多么不观察胚囊开发的公开混乱，显示Nanog起到在ICM和TE的分离的Oct4的一个谄媚的作用。

简介：Kr眉p像像素的因素8(KLF8)抄写因素在房间周期前进起一个关键作用，oncogenic转变，对间充质的转变和侵略上皮。然而，它的原子本地化信号(NLS)没被识别。有另外的KLFmonopartiteNLS(mNLS)和C2H2锌手指(ZF)的KLF8份额，哪个被显示了是为一些另外的KLF的NLS。在这份报告，用指导PCR的mutagenesis和immunofluorescent显微镜学，我们显示出mNLSs，任何单个ZF的删除，或变化的那混乱Zn2+有约束力或联系DNA主题没影响KLF8的原子本地化。删除>然而，从C终点的1.5ZF引起了KLF8的细胞质的累积。令人惊讶地，氨基酸(aa)的删除151-200区域几乎从原子核消除了KLF8。有PKC禁止者的S165A，K171E或K171R变化，或处理导致了部分细胞质的累积。Co-immunoprecipitation证明KLF8与importin-交往了，这个相互作用要求了ZF主题。aa1-150或201-261区域的删除独自没改变原子本地化。BrdU加入和cyclinD1倡导者酶试金作为野类型的KLF8证明在原子本地化的KLF8异种有缺陷者不能支持DNA合成或cyclinD1倡导者激活。一起拿，这些结果建议KLF8有二NLS，一包围S165和K171并且另外的是二双人脚踏车ZF，它为KLF8原子本地化和它的细胞的功能的规定是批评的。

简介：ErbB2,amemberofthereceptortyrosinekinasefamily,isfrequentlyover-expressedinbreastcancer.ProteolysisoftheextracellulardomainofErbB2resultsinconstitutiveactivationofErbB2kinase.RecentstudyreportedthatErbB2isfoundinthenucleus.Here,weshowedthatErbB2isimportedintothenucleusthroughanuclearlocalizationsignal(NLS)-mediatedmechanism.TheNLSsequenceKRRQQKIRKYTMRR(aa655-668)containsthreeclustersofbasicaminoacidsanditissufficienttotargetGFPintothenucleus.However,mutationinanybasicaminoacidclusterofthisNLSsequencesignificantlyaffectsitsnuclearlocalization.Furthermore,itwasfoundthatthisNLSisessentialforthenuclearlocalizationofErbB2sincetheintracellulardomainofErb2lackingNLScompletelyabrogatesitsnucleartranslocation.Takentogether,ourstudyidentifiedanovelnuclearlocalizationsignalandrevealsanovelmechanismunderlyingErbB2nucleartraffickingandlocalization.