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：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：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：铜绑定，抛锚膜的、细胞的prion蛋白质(PrPC)有二个组成的劈开地点生产不同N终端和C终端碎片(N1/C1和N2/C2)。用表示也人的PrPC，鼠标PrPC或鼠标PrPC的RK13房间带3F4epitope，这研究在endoproteolytic劈开和一个通常认为的PrPC函数上探索了PrPC主要顺序的影响，地图kinase信号transduction，响应外长的铜与或没有使不安的膜环境。PrPC主要顺序，特别在N1/C1劈开地点附近，看起来在这个地点和细胞外的调整信号的kinase1/2(ERK1/2)phosphorylation影响解朊作用的基础层次，与处理激活增加与基础ERK1/2表明一种反的关系。人的PrPC独自响应铜显示出增加的N1/C1劈开，由特定的p38和JNK/SAPKphosphorylation伴随了。到加扣押胆固醇的抗菌素filipin的铜的联合暴露导致了一只老鼠信号蛋白质phosphorylation的PrPC特定的实质的增加，由N1/C1劈开的增加伴随了。怀有人的N1/C1劈开地点的老鼠PrPC基础地并且响应铜假定更似人类的侧面并且改变了膜环境。我们的结果证明在N1/C1劈开地点附近的PrPC主要顺序影响在这个地点处理的endoproteolytic，它显得连接了基础地并且响应铜印射kinase信号transduction。进一步，主要顺序看起来响应外长的刺激在PrPC相关的信号transduction的忠实上授与N1/C1劈开和膜完整的相互的依赖。

简介：Thenorepinephrinetransporter(NET)isamemberoftheNa^+/Cl^-dependentneurotransmittertransporterfamilyandconstitutesthetargetofseveralclinicallyimportantantidepressants.TodelineatethecriticalaminoacidresiduesandthefunctionofC-terminalinregulatingtransportactivityofNET,hereweconstructedtwositemutants(V70F,F72V;V70I,F72V)andoneC-terminaltruncatedmutant(Δ611-617).ThewildtypeandmutantsofNETwereexpressedinXenopusoocytesbyinjectionoftheircRNA.Wefoundthatallofthesemutantslosttheirtransportactivity.TheseresultsindicatethattheaminoacidresiduesofV70andF72,andthelastsevenaminoacidsofC-terminalareessentialtothetransportactivityofNET.

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：氮的氧化物(没有)在neurodegeneration的提升被含有。然而，很少对在之间的关系被知道没有并且在neurodegenerative的神经干细胞(NSC)的自强或区别能力疾病。在这研究，我们调查了效果不，在在一个动物的NSC的自强上，为Niemann精选的模型打C(NPC)疾病。我们发现没有生产显著地从NPC1缺乏的老鼠(NPC1-/-)在NSC被增加，它显示出减少的NSC自强。nestin积极的房间的数字和neurospheres的尺寸显著地两个都被减少。没有synthase(NOS)的表达式在与野类型的neurospheres相比从NPC1-/-鼠标的大脑导出的neurospheres被增加。肝糖synthasekinase-3beta(GSK3beta)和caspase-3的不调停的激活也从NPC1-/-老鼠在NSC被观察。从NPC1-/-老鼠的NSC的自强能力被一个NOS禁止者恢复，L名字，它导致了GSK3beta和caspase-3的抑制。另外，NSC的区别能力部分被恢复并且Fluoro碧玉的数字C积极的堕落神经原被减少。这些数据建议那生产过剩不，在NPC，疾病损害了NSC的自强。没有生产的控制可能为NPC疾病的处理是关键的。

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：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.