
Type:Protein
SpeciesReactivity:H
B=Bovine;Ca=Cat;Ch=Chicken;D=Dog;EQ=Equine;GP=GuineaPig;H=Human;M=Mouse;P=Porcine;Pr=Primate;R=Rat;Rb=Rabbit;Y=Yeast;Xe=Xenopus;Ze=Zebrafish;;;;NA-NotApplicable;STP=Step-TactinProteins;AllGas1(GrowthArrestSpecific1)isoneofsixstructurallyunrelatedproteinsthatwereidentifiedbytheirincreasedexpressioningrowtharrestedcellsrelativetoactivelyproliferatingcells(1,2).Followingmitogenicstimulation,Gas1expressionistranscriptionallysuppressedbycMycascellstransitfromG0toG1phasesofthecellcycle(3,4).OverexpressionofGas1preventsSphaseentryandDNAsynthesis(5).Gas1mediatedblockadeofthecellcycleisp53dependentbutdoesnotrequirethetransactivatingdomainofp53(6).ThehumanGas1CDNAencodesa345aminoacid(aa)precursorthatincludesa39aasignalsequence,a279aamatureprotein,anda27aaCterminalpropeptide.Gas1containsAlarichandAsprichregionsaswellasanRGDsequence(5).MaturehumanandmouseGas1share85%aasequenceidentity.HumanGas1isa40kDaGPIlinkedglycoproteinthatisuniformlydistributedonthecellsurface(7).
Incontactinhibitedvascularendothelialcells,Gas1isinducedbyVECadherinandVEGFexpressionandmediatestheantiapoptoticeffectofVEGF(8).Incontrast,Gas1isinducedinhippocampalneuronsafterNMDAexposurebutfunctionsasaproapoptoticeffectorofNMDAmediatedexcitotoxicity(9).Gas1exhibitsarangeofdevelopmentalactionsincludingeitherpromotingorinhibitinggrowthanddifferentiationofsomite,limb,cerebellar,andeyetissues(1014).Gas1contributestotheantagoNISTiceffectofWntproteinstowardShhfunctionbybindingtheNterminalregionofShh(11).ThedependenceofGas1functiononthecellularcontexthasbeenaddressedbysuggestingthatGas1couldfunctionasacoreceptorforGDNFfamilyligands(15).
ebiomall.com






>
>
>
>
>
>
>
>
>
>
>
>
NaturalProteinStopsDeadlyHumanBrainCancerInMice
ScientistsfromJohnsHopkinsandfromtheUniversityofMilanhaveeffectivelyproventhattheycaninhibitlethalhumanbraincancersinmiceusingaproteinthatselectivelyinducespositivechangesintheactivityofcellsthatbehavelikecancerstemcells.ThereportispublishedinNature.
Themostcommontypeofbraincancer-glioblastoma-ismarkedbythepresenceofthesestem-cell-likebraincells,which,insteadoftriggeringthereplacementofdamagedcells,formcancertissue.Stemcells,unlikeallothercellsinthebody,arecapableofformingalmostanykindofcellwhentheright"signals"triggertheirdevelopment.
Fortheirtreatmentexperiment,theresearchersreliedonaclassofproteins,bonemorphogenicproteins,thatcauseneuralstem-cell-likeclusterstolosetheirstemcellproperties,whichinturnstopstheirABIlitytodivide.
Firsttheypretreatedhumanglioblastomacellswithbonemorphogenicprotein4(BMP4),theninjectedthesetreatedcellsintomousebrains.Inmiceinjectedwithcellsthatwerenotpretreated,large,invasivecancersgrew.InthemicewithBMP4-treatedcells,nocancersgrewatall.Threetofourmonthsafterinjection,allmicethatgotuntreatedcellsdied,andnearlyallmicewithBMP4-treatedcellswerealive.
Next,thescientistsdeliveredslow-releaseBMP4-containing"beads"directlyintomousebrainswithimplantedglioblastomacells.Micethatgotemptybeadsdevelopedlargemalignanttumorsanddied.MicewithBMP4beadssurvivedmuchlonger,and80percentsurvivedfourmonthsaftercancercellimplants.
"OurideaistotreatpatientswithBMP4orsomethinglikeitrightaftersurgerytoremoveglioblastomainhopesofpreventingtheregrowthofthecancerandimprovingsurvivaltime,"saysAlessandroOlivi,M.D.,directoroftheDivisionofNeurosurgicalOncologyatHopkinsandacontributortothestudy.
OlivisaysclinicalstudiesusingBMP4couldbeginwithinayearand,ifsuccessful,drugtherapiescouldbeavailabletothepublicwithinthreetofouryears.
"ThiswasproofoftheideathatBMPscouldstopglioblastomabydepletingthestem-cell-likepopulationthatfeedsit,"saysHenryBrem,M.D.,chairmanoftheDepartmentofNeurosurgeryatHopkinsandacollaboratorinthestudy."Thisopensexcitingdoorstofutureresearchintotreatmentsandtherapiesforsuchadevastatingdisease."

