简介：

简介：死亡联系域的蛋白质Daxx施加包括调停的许多报导功能经由激活c6月N终端从FasL发信号到apoptosisapoptosis的kinase(JNK)，正式就职和抑制，和染色质改变的规定。它原来从酵母被克隆用船边交货对相似物体之连续感觉而形成心像口的细胞内部的尾巴的二混血儿的屏幕诱饵。而许多起始的报告仍然保持争论，Daxx在一系列压力信号包括UVirradiation，过氧化氢治疗和TGF-β治疗触发的apoptosis的规定起重要作用，是清楚的。在这评论，我们在Axinbeing上集中连接Daxx到p53的一个拴住的因素。

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：在Saccharomycescerevisiae，必要基因CDC13编码telomeric遗传上并且身体上与Stn1p和Ten1p交往的搁浅单人赛的DNA有约束力的蛋白质，并且为telomere结束保护和telomere长度控制被要求。Ten1由参予telomere长度规定和染色体结束保护的分子的机制留下逃犯。在这个工作，我们用净化的recombinantCdc13p和Ten1p在胶化过滤分析观察了Cdc13p和Ten1p的一个弱相互作用。Ten1p本身展出一项弱DNA有约束力的活动，但是提高telomericTG1鈥吗？Cdc13p的DNA有约束力的能力。Cdc13p是有Ten1p的co-immunoprecipitated。在变异的ten1-55或ten1-66房间，在Ten1p和Cdc13p之间的损害相互作用与telomericDNA导致长得多的telomeres，以及Cdc13p的一个减少的协会。一致地，Ten1-55和Ten1-66异种蛋白质没能刺激telomeric在vitro的Cdc13p的DNA有约束力的活动。这些结果建议Ten1p提高telomericCdc13p到的DNA有约束力的活动否定地调整telomere长度。

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：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：TheundecapeptidesubstanceP(SP)wasshowntobeintimatelyinvolvedinboththestructuralandfunctionalaspectsoftheanteriorpituitary.Yet,inadditiontoitsinfluencesonhormonalsecretion,SPmaywellpossessmoreactionsinthismastergland.ThepresentstudywasfthereforeaimedtoinvestigatetheeffectofSPontheproliferationofratanteriorpituitarycellsinprimaryculture,ItwasfoundthatSPcoulddose-dependentlyincreasetheincorporationoftritiatedthymidine(3H-TdR)intoculturedanteriorpituitarycells.OthermammaliantachykininssuchasneurokininAandneurokininBhadsimilareffectbuttovaryingdegrees.TheequipotentanalogueofSP,Norleucine^11-SP(Nle^11-SP),alsoactedlikewise.withitsactionantagonizablebyspantide,aSPreceptorblocker.TofurthercharacterizethenatureofcellsresponsivetothechallengeofSP,immunocytochemicalstainingagainstS-100proteinandsomeadenohypophysealhormoneswasperformedaloneorplusautoradiography.TheresultsshowedthatthepercentageofS-100proteinimmunorectivecellswasapparentlyelevatedbytheaddtionofNle^11-Spfor48h,whichindicatesapreferentialproliferationoffolliculo-stellatecellsundertheregime.ThiswasconfirmedbyincreasesinimmunocytochemicalorautoradiographicallabellingindicesofanteriorpituitarySubstancePandanteriorpituitarycellproliferation.Cellstreatedsimilarly.Takentogether,TheseresultsrevealthatthetrophicactionofSPobservedpreviouslyinothertissuesisalsopresentatleastinculturedratanteriorpituitarycells.withrespondingcellsbeingpredominantlyfolliculo-stellatecellsastypifiedbyS-100proteinimmunoreactivity.Therefore,anintra-pituitarytrophicactionofSPinvivocouldbeanticipated.

简介：cAMPmediatedsignalingmayplayasuppressiveroleinimmuneresponse.WepreviouslyfoundthatthecAMP-elevators(CTxand8-Br-cAMP)inhibitedIL-12,IL-la,IL-6geneexpression,butincreasedthetranscriptionallevelsofIL-10andIL-1RainLPS-treatedmurineperitonealmacrophages.ThepresentstudyexaminedapossiblemolecularmechanisminvolvedincAMPelevators-inducedinhibitionofIL-12p40expressioninresponsetoLPS.OurdatademonstratedthatcAMPelevatorsdownregulatedIL-12p40mRNAexpressionandIL-12pT0productioninmurineperitonealmacrophages.SubsequentstudiesrevealedthatcAMP-elevatorsblockedphosphorylationofp38MAPK,butdidnotaffecttheactivityofNF-κBbindingtoIL-12promoter(-136/-112).ThisisthefirstreportthatcAMPelevatorsinhibitLPS-inducedIL-12productionbyamechanismthatisassociated,atleastinpart,withp38-dependentinhibitionbycAMPsignalingpathways.

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简介：TherearetwopossibleoutcomeswhenDNAdamageoccursinnormalmammaliancells:eitherinductionofcell-cyclecheckpointwhichinhibitstheprogressofthecellcyclesaswellasactivatesDNArepairpathways,oractivationofapoptosistoeliminatedamagedcells.Thep53tumour-suppressorgeneplaysakeyroleinselectingthesepathways.Inourpresentworks,thehumangastriccancercelllineAGSwastreatedwithtripchlorolide,apotentantitumorcompoundpurifiedfromaChineseherbTripterygiumWilfordiiHook.Singlecellgelelectrophoresis(Cometassay)showedthatthetreatmentoftripchlorolideresultedinDNAdamageinAGScells.ThedamagedAGScellswentthroughapoptosis,whichwastime-anddose-dependent.

简介：Recentstudiesindicatethatcell-cyclecheckpointsaretightlycorrelatedwiththeregulationofapoptosis,inwhichp53playsanimportantrole.OurpresentworksshowthattheexpressionofE6/E7oncogenesofhumanpapillomavirusinHeLacellsisinhibitedinthepresenceofanti-tumorreagenttripchlorolide(TC),whichresultsintheup-regulationofp53inHeLacells.Interestingly,underthesameTC-treatment,thecellsattheearlyS-phasearemoresusceptibletoapoptosisthanthoseatthemiddleS-phasealthoughp53proteinisstabilizedtothesamelevelinbothsituations.Significantdifferenceisexhibitedbetweenthetwospecifiedexpressionprofiles.Furtheranalysisdemonstratesthatanti-apoptoticgenesurvivinisup-regulatedbyp53intheTC-treatedmiddle-Scells,whereasitisdown-regulatedbyp53intheTC-treatedearly-Scells.Takentogether,thepresentstudyindicatesthatthedifferentialp53-regulatedexpressionofsurvivinatdifferentstagesofthecellcycleresultsindifferentcellularoutputsunderthesameapoptosis-inducer.

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。

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简介：CREB有约束力的蛋白质(CBP)和它的相当或相同事物p300是涉及细胞的活动的一个宽数组的各种各样的顺序特定的抄写因素的transcriptionalco使活跃之物，例如脱氧核糖核酸修理，房间生长，区别和apoptosis。Severalstudies建议了CBP和p300可能被看作瘤压制ors，与他们是的突出的角色响应各种各样的刺激的不同基因表示模式的跨coupling。他们主要经由乙酰化施加行动嘘和另外的规章的蛋白质(例如p53)。在CBP/p300功能的主要悖论是他们似乎能够贡献各种各样的反对细胞的进程。呼吸上皮tumorigenesis代表一个范围的多步累积的一个复杂过程基因并且epigenetic错误。通过激活和压抑的建筑群的交替的形成的Transcriptionmodulation是这些精神错乱的最终的收敛点，并且CBP/p300在这相互影响代表关键参加者。因此，他们的分子的行动和相互作用的照明能在呼吸上皮carcinogenesis为药理学干预揭示新潜在的目标。

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：Changesinthedistributionof1P1-antigeninthedevelopingchickretinahavebeenexaminedbyindriectimmunofluorescencestainingtechniqueusingthenovelmonoclonalantibody(MAb)1P1.Expressionofthe1P1antigenwasfoundtoberegulatedinradialaswellasintangentialdimensionoftheretina,beingpreferentiallyorexclusivelylocatedintheinnerandouterplexiformlayersoftheneuralretinadependingonthestagesofdevelopment,Withtheonsetoftheformationoftheinnerplexiformlayer1P1antigenbecomesexpressedintheretina.Withprogressingdifferentiationoftheinnerplexiformlayer1P1immunofluorescencerevealed2subbandsatE9and6subandsatE18,Atpostnatalstages(afterP3)immunoreactivitywasreducedinaninside-outsidesequenceleadingtothecompleteabsenceofthe1P1antigeninadulthood.1P1antigenexpressionintheouterplexiformlayerwasalsosubjecttodevelopmentalregulation.Thespation-temporalpatternof1P1antigenexpressionwascorrelatedwiththetimecourseofhistologicaldifferentationofchickretina,namelythesynapserichplexiformlayers.Whetherthe1P1antigenwasfunctionallyinvolvedindendriteextensionandsynapseformationwasdiscussed.

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

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

简介：WereportedinthismanuscriptthatTGF-β1inducesapoptosisinAML12murinehepatocytes,whichisassociatedwiththeactivationofp38MAPKsignalingpathway.SB202190,aspecificinhibitorofp38MAPK,stronglyinhibitedtheTGF-β1-inducedapoptosisandPAI-1promoteractivity.TreatmentofcellswithTGF-β1activatesp38.Furthermore,over-expressionofdominantnegativemutantp38alsoreducedtheTGF-β1-inducedapoptosis.Thedataindicatethattheactivationofp38isinvolvedinTGF-β1-mediatedgeneexpressionandapoptosis.