Gas1(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).
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