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: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: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:Amajorproblemwhichispoorlyunderstoodinthemanagementofbladdercancerislowsensitivitytochemotherapyandhighrecurrenceaftertransurethralresection.Insulin-likegrowthfactor1receptor(IGF-1R)signalingplaysaveryimportantroleinprogression,invasionandmetastasisofbladdercancercells.Inthisstudy,weinvestigatedwhetherIGF-1Rwasinvolvedinthegrowthstimulatingactivityanddrugresistanceofbladdercancercells.Theresultsshowed:ThemRNAsofIGF-1,IGF-2andIGF-1Rwerestronglyexpressedinserum-freeculturedT24cellline,whereasnormalurothelialcellsdidnotexpressthesefactors/receptorsoronlyintracelevels;T24cellrespondedfarbettertogrowthstimulationbyIGF-1thandidnormalurothelialcells;blockageofIGF1Rbyantisenseoligodeoxynucleotide(ODN)significantlyinhibitedthegrowthofT24cellandenhancedsensitivityandapoptosisofT24cellstomitomycin(MMC).TheseresultssuggestedthatblockageofIGF-IRsignalingmightpotentiallycontributetothetreatmentofbladdercancercellswhichareinsensitivetochemotherapy.
简介:<正>WeandothershavefirmlyestablishedthatsurfaceIgMreceptor(sIgM-R)crosslinkingwithantibodiestotheiheavychain(anti-i)leadstogrowtharrestandapoptosisinaseriesofwellcharacterizedB-celllymphomas.Thisrequiresablationofc-Mycproteinexpressionandtheconcomitantinductionofthecyclin-dependent-kinaseinhibitor,p27Kip1.Thesignalingmechanismsregulatingc-Mycandp27Kip1proteinexpressionarepoorlyunderstood.However,werecentlyestablishedthatsIgM-Rmediateddown-modulationofthePI-3Kpathwaydirectlyaffectedc-Mycandp27Kip1expressionandaccuratelypredictedgrowtharrest