EntrezGeneSummary | Thisgeneencodestumorproteinp53,whichrespondstodiversecellularstressestoregulatetargetgenesthatinducecellcyclearrest,apoptosis,senescence,DNArepair,orchangesinmetabolism.p53proteinisexpressedatlowlevelinnormalcellsandatahighlevelinavarietyoftransformedcelllines,whereit"sbelievedtocontributetotransformationandmalignancy.p53isaDNA-bindingproteincontainingtranscriptionactivation,DNA-binding,andoligomerizationdomains.Itispostulatedtobindtoap53-bindingsiteandactivateexpressionofdownstreamgenesthatinhibitgrowthand/orinvasion,andthusfunctionasatumorsuppressor.Mutantsofp53thatfrequentlyoccurinanumberofdifferenthumancancersfailtobindtheconsensusDNAbindingsite,andhencecausethelossoftumorsuppressoractivity.Alterationsofthisgeneoccurnotonlyassomaticmutationsinhumanmalignancies,butalsoasgermlinemutationsinsomecancer-pronefamilieswithLi-Fraumenisyndrome.Multiplep53variantsduetoalternativepromotersandmultiplealternativesplicinghavebeenfound.Thesevariantsencodedistinctisoforms,whichcanregulatep53transcriptionalactivity.[providedbyRefSeq] |
UniProtSummary | FUNCTION:SwissProt:P04637#Actsasatumorsuppressorinmanytumortypes;inducesgrowtharrestorapoptosisdependingonthephysiologicalcircumstancesandcelltype.Involvedincellcycleregulationasatrans-activatorthatactstonegativelyregulatecelldivisionbycontrollingasetofgenesrequiredforthisprocess.Oneoftheactivatedgenesisaninhibitorofcyclin-dependentkinases.ApoptosisinductionseemstobemediatedeitherbystimulationofBAXandFASantigenexpression,orbyrepressionofBcl-2expression. COFACTOR:Binds1zincionpersubunit. SIZE:393aminoacids;43653Da SUBUNIT:InteractswithAXIN1.ProbablypartofacomplexconsistingofTP53,HIPK2andAXIN1(Bysimilarity).BindsDNAasahomotetramer.InteractswithhistoneacetyltransferasesEP300andmethyltransferasesHRMT1L2andCARM1,andrecruitsthemtopromoters.Invitro,theinteractionofTP53withcancer-associated/HPV(E6)viralproteinsleadstoubiquitinationanddegradationofTP53givingapossIBLemodelforcellgrowthregulation.Thiscomplexformationrequiresanadditionalfactor,E6-AP,whichstablyassociateswithTP53inthepresenceofE6.C-terminusinteractswithTAF1,whenTAF1ispartoftheTFIIDcomplex.InteractswithING4andthisinteractionmaybeindirect.FoundinacomplexwithCABLES1andTP73.InteractswithHIPK1,HIPK2,andP53DINP1.InteractswithWWOX.MayinteractswithHCVcoreprotein.InteractswithUSP7andSYVN1.InteractswithHSP90AB1(Bysimilarity).InteractswithBANP. SUBCELLULARLOCATION:Cytoplasm.Nucleus.Endoplasmicreticulum.Note=InteractionwithBANPpromotesnuclearlocalization. DOMAIN:SwissProt:P04637Thenuclearexportsignalactsasatranscriptionalrepressiondomain. PTM:Acetylated.AcetylationofLys-382byCREBBPenhancestranscriptionalactivity.DeacetylationofLys-382bySIRT1impairsitsabilitytoinduceproapoptoticprogramandmodulatecellsenescence.&PhosphorylationonSerresiduesmediatestranscriptionalactivation.PhosphorylatedbyHIPK1(Bysimilarity).PhosphorylatedonThr-18byVRK1,whichmaypreventtheinteractionwithMDM2.PhosphorylatedonThr-55byTAF1,whichpromotesMDM2-mediateddegradation.PhosphorylatedonSer-46byHIPK2uponUVirrADIation.PhosphorylationonSer-46isrequiredforacetylationbyCREBBP.PhosphorylatedonSer-392followingUVbutnotgammairradiation.PhosphorylateduponDNAdamage,probablybyATMorATR.PhosphorylatedonSer-15uponultravioletirradiation;whichisenhancedbyinteractionwithBANP.&DephosphorylatedbyPP2A.SV40smallTantigeninhibitsthedephosphorylationbytheACformofPP2A.&MaybeO-glycosylatedintheC-terminalbasicregion.StudiedinEB-1cellline.&UbiquitinatedbySYVN1,whichleadstoproteasomaldegradation. DISEASE:SwissProt:P04637#TP53isfoundinincreasedamountsinawidevarietyoftransformedcells.TP53isfrequentlymutatedorinactivatedinabout60%ofcancers.&DefectsinTP53areinvolvedinesophagealsquamouscellcarcinoma(ESCC)[MIM:133239].ESCCisatumoroftheesophagus.&DefectsinTP53areacauseofLi-Fraumenisyndrome(LFS)[MIM:151623].LFSisanautosomaldominantfamilialcancersyndromethatinitsclassicformisdefinedbytheexistenceofbothaprobandwithasarcomaandtwootherfirst-degreerelativeswithacancerbyage45years.Inthesefamiliestheaffectedrelativesdevelopadiversesetofmalignanciesatunusuallyearlyages.ThespectrumofcancersinLFSincludesbreastcarcinomas,soft-tissuesarcomas,braintumors,osteosarcoma,leukemiaandadreno-corticalcarcinoma.OtherpossiblecomponenttumorsofLFSaremelanoma,gonadalcelltumorsandcarcinomasofthelung,pancreasandprostate.&DefectsinTP53maybeassociatedwithnasopharyngealcarcinoma[MIM:161550];alsoknownasnasopharyngealcancer.&DefectsinTP53arefoundinBarrettmetaplasia;alsoknownasBarrettesophagus.Itisaconditioninwhichthenormallystratifiedsquamousepitheliumoftheloweresophagusisreplacedbyametaplasticcolumnarepithelium.Theconditiondevelopsasacomplicationinapproximately10%ofpatientswithchronicgastroesophagealrefluxdiseaseandpredisposestothedevelopmentofesophagealadenocarcinoma.&DefectsinTP53areinvolvedinheadandnecksquamouscellcarcinomas(HNSCC)[MIM:275355].&DefectsinTP53areinvolvedinoralsquamouscellcarcinoma(OSCC).Cigarettesmokeisaprimemutagenicagentincanceroftheaerodigestivetract.&DefectsinTP53areacauseoflungcancer[MIM:211980].&DefectsinTP53areacauseofchoroidplexuspapilloma[MIM:260500].Choroidplexuspapillomaisaslow-growingbenigntumorofthechoroidplexusthatofteninvadestheleptomeninges.Inchildrenitisusuallyinalateralventriclebutinadultsitismoreofteninthefourthventricle.Hydrocephalusiscommon,eitherfromobstructionorfromtumorsecretionofcerebrospinalfluid.Ifitundergoesmalignanttransformationitiscalledachoroidplexuscarcinoma.Primarychoroidplexustumorsarerareandusuallyoccurinearlychildhood.&DefectsinTP53areacauseofoneformofhereditaryadrenocorticalcarcinoma(ADCC)[MIM:202300].ADCCisararechildhoodtumor,representingabout0.4%ofchildhoodtumors,withahighincidenceofassociatedtumors.ADCCoccurswithincreasedfrequencyinpatientswiththeBeckwith-Wiedemannsyndrome[MIM:130650]andisacomponenttumorinLi-Fraumenisyndrome[MIM:151623]. SIMILARITY:Belongstothep53family. |