简介：混合的系kinase(MLK3)3是被肿瘤坏死因素激活的激活mitogen的蛋白质kinasekinasekinase--伪(TNF-伪)并且明确地在TNF-伪刺激上激活c6月N终端kinase(JNK)。TNF-伪由激活MLK3的机制不被知道。TNF联系受体的因素(TRAF)是被招募到TNF受体的细胞质的结束并且调停的改编者分子，包括JNK的激活下游的发信号。这里，我们报导MLK3与TRAF2，TRAF5和TRAF6联系；然而，仅仅TRAF2能显著地导致MLK3的kinase活动。到TRAF领域并且为到它的C终端一半(氨基酸511-847)的MLK3的TRAF2地图的相互作用领域。与对方一起的内长的TRAF2和响应以一种时间依赖者方式的TNF-伪处理的MLK3伙伴。在MLK3和TRAF2之间的协会调停有绑在MLK3的TRAF2删除异种的MLK3激活和竞争以一种剂量依赖者方式稀释MLK3kinase活动，在TNF-伪处理上。而且MLK3的下游的目标，JNK被TNF-伪以一种TRAF2依赖的方式激活。因此，我们在TRAF2和MLK3之间的直接相互作用为TNF-伪-被要求的数据表演导致了MLK3和它的下游的目标的激活，JNK。

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.

简介：hPFTAIRE1(PFTK1)，Cdc2相关的蛋白质kinase，高度在人的大脑被表示。它在Hela房间展出细胞质的分发，尽管它在它的N终点包含二个原子本地化信号(NLS)。到为它的底层和规章的部件的搜索，我们由把全身的hPFTAIRE1用作一个诱饵屏蔽了一个二混血儿的图书馆。四14-3-3isoforms(贝它，epsilon，希腊语字母的第七字，字形物)被识别与hPFTAIRE1交往。我们在hPFTAIRE1发现了一个通常认为的14-3-3绑定一致主题(RHSSPSS)，它与它的第二NLS重叠了。RHSSPSS主题的删除或有在保存有约束力的主题的翼的Ser119的替换废除了在hPFTAIRE1和14-3-3蛋白质之间的特定的相互作用。变异的S120AhPFTAIRE1也显示出一个弱相互作用到14-3-3蛋白质。结果建议Ser119为在hPFTAIRE1和14-3-3蛋白质之间的相互作用是关键的。当熔化了到绿荧光灯的蛋白质(GFP)的C终点时，所有hPFTAIRE1异种在Hela房间和人的neuroblastoma房间(SH-SY5Y)的细胞质散布了，显示有14-3-3蛋白质的那绑定不贡献潜水艇hPFTAIRE1的细胞的本地化，尽管绑定可以涉及它的发信号的规定。

简介：Amurinemacrophage-likecelllineJ774,acquired,inresponsetoLPS,anabilitytokilltumornecrosisfactor(TNF)-insensitivetargetP815mastocytomacellswhereasanothercellline,P388D1didnot,LPStriggeredsignalingmechanismsbetweenthetwocelllineswerecomparedwithanaimtoinquireaboutthepossiblenatureoftheabove-mentioneddifference,TheresultswhowedthattwocelllinesrespondtoLPS-treatmentbyparallelactivationofbothphospholipasesCandA2(PLCandPLA2)toapproximatelythesameextent.ThemaximumresponseoftothenzymesofJ774cellswasnotedwithin10minthetreatmentwhereasthatofP388D1cellsrequiredmorethan20min,TheotherpropertiesofLPS-responsiveenzymesstudiedweresimilarbetweentwocelllines,includingActivationofPLCandPLA2andPKCinmacrophagesbyLPS.Ca2+augmentationofenzymeactivation,participationofguaninenucleotidebinding(G)proteinsintheinitialactivationpreocesses,andinhibitionofenzymeactivationbythepriortreatmentofcellswithcholeraorpertussistoxinsetc.Moreover,LPS-triggeredactivationofPLCandPLA2wasfoundtobefollowedbytheincreaseofPKCactivitiesinbothcelllines.Inspiteofthesesimilarities.J774cellspossessedbothbasicandacidicformsofPKCactivities,whileP388D1cellsownedonlyPKCofbasicform,Nevertheless,thequestionwhyJ774cellsbutnotP388D1cells,canacquirethetumoricidalactivity,aganistP815,cellsfollowingLPStreatmentrematinstobeanswered.

简介：Thec-erbB-2proto-oncogeneencodesa185kDaproteinp185,whichbelongstoepidermalgrowthfactorreceptorfamily.Amplificationofthisgenehasbeenshowntocorrelatewithpoorclinicalprognosisforcertaincancerpatients.ThemonoclonalantibodyA21whichdirectedagainstp185specificallyinhibitsproliferationoftumorcellsoverexpressingp185,henceallowsittobeacandidatefortargetedtherapy.InordertoovercomeseveraldrawbacksofmurineMAb,wecloneditsVHandVLgenesandconstructedthesingle-chainFv(scFv)throughapeptidelinker.TherecombinantscFvA21wasexpressedinEscherichiacoliandpurifiedbytheaffinitycolumn.SubsequentlyitwascharacterizedbyELISA,Westernblot,cellimmunohistochemistryandFACS.Alltheseassaysshowedthebindingactivitytoextracellulardomain(ECD)ofp185.BasedonthosepropertiesofscFvA21,wefurtherconstructedthescFv-Fcfusionmoleculewithahomodimerformandtherecombinantproductwasexpressedinmammaliancells.Inaseriesofsubsequentanalysisthisfusionproteinshowedidenticalantigenbindingsiteandactivitywiththeparentantibody.Theseanti-p185engineeredantibodieshavepromisedtobefurthermodifiedasatumortargetingdrugs,withaviewofapplicationinthediagnosisandtreatmentofhumanbreastcancer.

简介：

简介：小道，肿瘤坏死因素相关的导致apoptosisligand，是一个新奇有势力通过房间表面死亡受体Trail-R1和Trail-R2的激活的房间死亡小径的内长的使活跃之物。它的角色象在导致激活的房间死亡(AICD)的FasL一样，在免疫系统被表明了。然而，小道的机制导致了apoptosis遗体不清楚。在这份报告，重组体小道蛋白质被表示并且净化。导致apoptosis活动和JurkatT房间上的重组体小道的规定机制是探索试管内。Trypan蓝排除试金证明重组体小道蛋白质活跃地以一种剂量依赖者方式杀死了JurkatT房间。在JurkatT房间的导致小道的apoptosis被Bcl-2显著地在Bcl-2基因transfected房间在表示上减少。有PMA(phorbol12十四酸盐13醋酸盐)的处理，PKC使活跃之物，在JurkatT房间的压制的导致小道的apoptosis。由PMA的apoptosis的抑制被预告的处理与二度废除，一个PKC禁止者。总起来说，Bcl-2在表示上和PMA激活PKC，这被建议活跃地下面调整在JurkatT的调停小道的apoptosis房间。

简介：导致死亡的肿瘤坏死的能力因素相关的导致apoptosisligand(小道)大部分被描述了有选择地杀死许多癌症房间，但是有治疗的主要担心之一是药抵抗和可能的有毒的副作用的出现。这里，我们报导那条小道在Jurkat和SUPT1T房间线并且在人的高强风然而并非在健康的导出题目的外部血mononuclear房间导致apoptosis。在平行，有小道和Tyrphostin(AG-490)的治疗，选择Januskinase2禁止者，生产cytotoxicity的明显的改进，与控制相比或到由Stat3phosphorylation的重要抑制描绘了落后于独自一个对待的样品，并且与cIAP-1和cIAP-2mRNA层次的戏剧的减少联系了。由特定的小干扰RNA的cIAP-1和cIAP-2的Downregulation显著地放大减少小道的cytotoxicity。所有一起，这些调查结果强烈显示cIAP-1和cIAP-2downregulation是在调停的发信号的小径的基本的步T上的小道和AG-490的组合效果房间白血病。这些调查结果可以帮助在小道敏感的白血病影响的病人的治疗为不太有毒的药理学策略的发展打开新线路。

简介：MYB蛋白质在真核细胞的有机体起重要作用。在植物，R1R2R3类型MYB蛋白质在房间周期控制工作。然而，R2R3类型MYB蛋白质是否也涉及房间部门过程，仍然保持未知。这里，我们报导那R2R3类型抄写因素基因，AtMYB59，涉及房间周期前进和根生长的规定。AtMYB59蛋白质在洋葱的原子核是局部性的表皮的房间并且transactivation活动。在酵母房间的AtMYB59的表示压制房间增长，和transformants与更长的房间有更多的原子核和更高的aneuploidDNA内容。在AtMYB59的保存领域的变化在酵母细胞生长上废除它的效果。在同步Arabidopsis房间暂停，AtMYB59基因明确地在房间周期前进期间在S阶段被表示。表示和promoter-GUS分析表明AtMYB59基因富有地在根被表示。转基因的植物overexpressingAtMYB59更短的根与野类型的植物(Arabidopsis就职Col-0)相比，并且在在根尖端的有丝分裂的房间的一半附近在中期。相反地，空变异的myb59-1比关口在中期让更长的根和更少有丝分裂的房间，建议那AtMYB59可以由扩大有丝分裂的房间的中期禁止根生长。AtMYB59调整许多下游的基因，包括CYCB1；1基因，可能通过到MYB应答的元素的绑定。这些结果在细胞周期规定和植物根生长为AtMYB59支持一个角色。

简介：

简介：CCAAT/enhancer有约束力的蛋白质α(C/EBPα)是transcriptional禁止细胞增殖的规章的因素，和其他的翻译开始生产二多肽，C/EBPαp30并且C/EBPαp42。由表示介绍，C/EBPαp30specifically禁止了基因的一个唯一的集合，这被揭示，包括MPP11，p84N5和SMYD2，它没被C/EBPαp影响42在两根QSG-7701hepatocyte房间线和QGY-7703hepatoma，cells.Semi量的RT-PCR分析独立地证实了这些结果。Chromatinimmunoprecipitation试金显示出30比C/EBPαp更强烈绑了在这些基因的倡导者的那C/EBPαp42。在C/EBPα是调整的down的临床的hepatoma在样品，所有三基因明确地由30在上面的C/EBPαp禁止了调整。然而，MPP11，p84N5和SMYD2genes的压抑可能直接不涉及C/EBPαp30-mediated生长抑制。我们的数据建议30调整的那C/EBPαp目标基因的一个唯一的集合并且多于C/EBPαp的dominant-negativeregulator42。

简介：组蛋白甲基化是参予细胞的过程的一个多样的数组的重要epigenetic现象并且被发现了与癌症被联系。几的Recentidentification嘘一demethylases证明了那嘘一甲基化是一个可逆过程。通过一条候选人途径，我们化学上有简历作为H3K27demethylase识别了JMJD3。进HeLa房间的JMJD3的Transfection引起了整齐的乙醇H3K27的特定的减小，但是没在di-和单音的甲基H3K27上有效果，或嘘H3K4和H3K9上的一离氨酸methylations。Theenzymatic活动要求JmjC域和被建议了为余因子绑定重要的保存组氨酸。试管内生物化学的实验证明那JMJD3directly催化demethylation。另外，我们发现JMJD3起来在前列腺癌症，和它的表示调整了在变形前列腺癌症是更高的。因此，我们作为能够把整齐的乙醇组从移开的ademethylase识别了JMJD3嘘一H3离氨酸27并且起来在前列腺癌症调整了。

简介：Amurinemacrophage-likecellline,J774,acquried,inresponsetoLPS,anabilitytokilltumornecrosisfactor（TNF）-insensitivetargetP815mastocytomacells,whereasanothercellline,P388D1,didnot.LPS-triggeredsignalingmechanismsbetweenthetwocelllineswerecomparedwithanaimtoinquireaboutthepossiblenatureoftheabove-mentioneddifference.TheresultsshowedthattwocelllinesrespondtoLPS-treatmentbyparallelactivationofbothphospholipasesCandA2（PLCandPLA2）toapproximatelythesameextent.ThemaximumresponseofbothenzymesofJ774cellswasnotedwithin10minofthetreatment,whereasthatofP388D1cellsrequiredmorethan20min.TheotherpropertiesofLPS-responsiveenzymesstudiedweresimilarbetweentwocelllines,ineludingActivationofPLCandPLA2andPKCinmacrophagesbyLPSCa2+augmentationofenzymeactivation,participationofguaninenucleotidebinding（G）proteinsintheinitialactivationprocesses,andinhibitionofenzymeactivationbythepriortreatmentofcellswithcholeraorpartussistoxinsetc.Moreover,LPS-triggeredactivationofPLCandPLA2wasfoundtobefollowedbytheincreaseofPKCactivitiesinbothcelllines.Inspiteofthesesimilarities,J774cellspossessedbothbasicandacidicformsofPKCactivities,whileP388D1cellsownedonlyPKCofbasicform.Nevertheless,thequestionwhyJ774cells,butnotP388D1cells,canacquirethetumoricidalactiyity,aganistP815cellsfollowingLPS-treatmentremainstobeanswered.

简介：ThemuscleproteinmyosinbindingproteinC(MyBPC)isalargemulti-domainproteinwhoseroleinthesarcomereiscomplexandnotyetfullyunderstood.MutationsinMyBPCarestronglyassociatedwiththeheartdiseasefamilialhypertrophiccardiomyopathy(FHC)andtheseexperimentsofnaturehaveprovidedsomeinsightintotheintricateworkingsofthisproteinintheheart.WhilesomeregionsoftheMyBPCmoleculehavebeenassignedafunctionintheregulationofmusclecontraction,theinteractionofotherregionswithvariouspartsofthemyosinmoleculeandthesarcomericproteins,actinandtitin,remainobscure.Inadditicn,severalintra-domaininteractionsbetweenadjacentMyBPCmoleculeshavebeenidentified.Althoughthebasicstructureofthemolecule(aseriesofimmunoglobulinandfibronectindomains)hasbeenelucidated,theassemblyofMyBPCinthesarcomereisatopicfordebate.ByanalysingtheMyBPCsequencewithrespecttoFHC-causingmutationsitispossibletoidentifyindividualresiduesorregionsofeachdomainthatmaybeimportanteitherforbindingorregulation.Thisreviewlooksatthecurrentliterature,inconcertwithalignmentsandthestructuralmodelsofMyBPC,inanattempttounderstandhowFHCmutationsmayleadtothediseasestate.

简介：在胸腺的中央忍耐是为删除汽车的主要机制反应T房间。尽管有这，进圆周的自我反应的T淋巴细胞的逃跑揭示汽车免疫的威胁。补偿它的瑕疵，胸腺也与镇压功能生产Foxp3+CD4+CD25+规章的T房间的一个自然地发生的子集，能够控制汽车反应房间。Foxp3(叉头框P3)，为房间的这个子集的系特定的标记，对他们的thymic开发和外部功能关键，并且还Foxp3驾驶的transcriptional程序直到现在大部分未定义。新兴的证据提供了卓见进它的角色：从Foxp3到的能力与象NFAT那样的另外的抄写因素合作，到目标的染色体宽的描述，基因直接由Foxp3跳了并且调整。这里，我们讨论自然地发生的规章的T房间的发现-他们的显型，发展，维护，和功能-大部分当他们被系特定的标记定义，Foxp3。

简介：<正>Asoneofthemostcharacterizedcytokines,interleukin3(IL-3)iswellknownforitssurvivaleffectonbothprogenitorsandmaturebloodcells.Althoughwiththeextensivestudies,thesignalingpathwaysandunderlyingmechanismleadingtosurvivalresponsesofIL-3stillarenotcompletelyunderstood.Recently,anapoptoticgeneticpathwayofC.eleganswassuggestedtobeevolutionallyconservedinthatcontrolsthecytokine-dependentanti-apoptoticresponsesinmammalianhematopoieticcelllineages.Amongthispathway,Ces-2isknowntobethefirstdeathspecificationgeneintheC.eleganspathwayandencodesabZIPfamilytranscriptionalfactorthatsharesthesameDNArecognitionsequencewithanoncoprotein,

简介：Glucosetransporter4(GLUT4)isresponsibleforinsulin-stimulatedglucosetransportingintotheinsulin-sensitivefatandmusclecells.ThedynamicsofGLUT4storagevesicles(GSVs)remainstobeexploredanditisunclearhowGSVsarearrangedbasedontheirmobility.Weexaminedthisissuein3T3-L1cellsviainvestigatingthethree-dimensionalmobilityofsingleGSVlabeledwithEGFP-fusedGLUT4.Athinlayerofcytosolrightadjacenttotheplasmamembranewasilluminatedandsuccessivelyimagedat5Hzunderatotalinternalreflectionfluorescencemicroscopewithapenetrationdepthof136nm.Employingsingleparticletracking,thethree-dimensionalsubpixeldisplacementofsingleGSVwastrackedataspatialprecisionof22nm.Boththemeansquaredisplacementandthediffusioncoefficientwerecalculatedforeachvesicle.Trackingresultsrevealedthatvesiclesmovedasifrestrictedwithinacagethathasameanradiusof160nm,suggestingthepresenceofsomeintracellulartetheringmatrix.ByconstructingthehistogramofthediffusioncoefficientsofGSVs,weobservedasmoothdistributioninsteadoftheexistenceofdistinctgroups.TheresultindicatesthatGSVsaredynamicallyretainedinacontinuousandwiderangeofmobilityratherthanintoseparateclasses.

简介：OverexpressionandactivationofHER-2/neu(alsoknownasc-erbB-2),aproto-oncogene,wasfoundinabout30%ofhumanbreastcancers,promotingcancergrowthandmakingcancercellsresistanttochemo-andradio-therapy.Wild-typep53iscrucialinregulatingcellgrowthandapoptosisandisfoundtobemutatedordeletedin60-70%ofhumancancers.Andsomecancerswithawild-typep53donothavenormalp53function,suggestingthatitisimplicatedinacomplexprocessregulatedbymanyfactors.Inthepresentstudy,weshowedthattheoverexpressionofHER-2/neucoulddecreasetheamountofwild-typep53proteinviaactivatingPI3Kpathway,aswellasinducingMDM2nucleartranslocationinMCF7humanbreastcancercells.BlockageofPI3KpathwaywithitsspecificinhibitorLY294002causedG1-Sphasearrest,decreasedcellgrowthrateandincreasedchemo-andradio-therapeuticsensitivityinMCF7cellsexpressingwild-typep53.However,itdidnotincreasethesensitivitytoadriamycininMDA-MB-453breastcancercellscontainingmutantp53.OurstudyindicatesthatblockingPI3KpathwayactivationmediatedbyHER-2/neuoverexpressionmaybeusefulinthetreatmentofbreasttumorswithHER-2/neuoverexpressionandwild-typep53.

简介：CT120,anovelmembrane-associatedgeneimplicatedinlungcarcinogenesis,waspreviouslyidentifiedfromchromosome17pl3.3locus,ahotmutationspotinvolvedinhumanmalignancies.Inthepresentstudy,wefurtherdeterminedthatCT120ectopicexpressioncouldpromotecellproliferationactivityofNIH3T3cellsusingMTSassay,andmonitoredthedownstreameffectsofCT120inNIH3T3cellswithAtlasmousecDNAexpressionarrays.Among588knowngenes,133geneswerefoundtobeupregulatedordownregulatedbyCT120.Twomajorsignalingpathwaysinvolvedincellproliferation,cellsurvivalandanti-apoptosiswereoverexpressedandactivatedinresponsetoCT120:OneistheRaf/MEK/ErksignalcascadesandtheotheristhePI3K/Aktsignalcascades,suggestingthatCT120mightcontribute,atleastinpart,totheconstitutivelyactivationofErkandAktinhumanlungcanercells.Inaddition,sometumormetastasisassociatedgenescathepsinB,cathepsinD,cathepsinL,MMP-2/TIMP-2werealsoupregulatedbyCT120,uponwhichCT120mightbeinvolvedintumorinvasivenessandmetastasis.Inaddition,CT120mightplayanimportantroleintumorprogressionthroughmodulatingtheexpressionofsomecandidate“LungTumorProgression”genesincludingB-Raf,Rab-2,BAX,BAG-1,YB-1,andCdc42.

简介：Galα(1,3)Gal(galepitope)isacarbohydrateepitopeandsynthesizedinlargeamountbyα(1,3)galactosyltransferase[α(1,3)GT]enzymeonthecellsoflowermammaliananimalssuchaspigsandmice.Humanhasnogalepitopeduetotheinactivationofα(1,3)GTgenebutproducesalargeamountofantibodies(anti-Gal)whichrecognizeGalα(1,3)Galstructuresspecifically.Inthisstudy,areplicationdeficientrecombinantadenoviralvectorAd5sGTcontainingpigα(1,3)GTcDNAwasconstructedandcharacterized.Adenoviralvector-mediatedtransferofpigα(1,3)GTgeneintohumantumorcellssuchasmalignantmelanomaA375,stomachcancerSGC-7901,andlungcancerSPC-A-1wasreportedforthefirsttime.ResultsshowedthatGalepitopedidnotincreasethesensitivityofhumantumorcellstohumancomplement-mediatedlysis,althoughhumancomplementactivationandthebindingofhumanIgGandIgMnaturalantibodiestohumantumorcellswereenhancedsignificantlyafterAd5sGTtransduction.AppearanceofgalepitopeonthehumantumorcellschangedtheexpressionofcellsurfacecarbohydratesreactingwithUlexeuropaeusI(UEAI)lectins,Viciavillosaagglutinin(VVA),Arachishypogaeaagglutinin(PNA),andGlycinemaxagglutinin(SBA)todifferentdegrees.Inaddition,noeffectofgalepitopeonthegrowthinvitroofhumantumorcellswasobservedinMTTassay.