p73基因在血液系统恶性肿瘤中的生物学行为

1p731997Kaghad11p36.2-3、、.p73［1］.p73［2］.p73、.p73.1p731.1p73p73p63p53p53.p7360kb14.p736TAPRDNADBDODα-SAMSAM.p73p53DBDp731，2，1*1．4100782.046000：p73p53，.p73、，p73，、.：p73；；；：R733：A：1007-7847（2009）01-0091-04TheBiologicalCharacteristicsofp73inHematologicalMalignanciesPEIJin-hong12HUWei-xin1*1.MolecularBiologyResearchCenterSchoolofBiologicalScienceandTechnologyCentralSouthUniversityChangsha410078HunanChina2.DepartmentofBiochemistryChangzhiMedicalCollegeChangzhi046000ShanxiChina：2008-07-11：[e-mail]*[e-mail]@hotmail.com.AbstractThep73geneanewmemberoftumorsuppressorgenep53familygivesrisetomultipleproteinisoformswithdifferentfunctions.Thestructureandfunctionsofp73proteinsaswellasbiologicalroleinhematologicalmalignanciesarereviewedinordertoexplorecorrelationbetweenp73andhematologicalmalignanciesthusrenderingarationalefordiagnosistherapyandprognosisofhematologicalmalignancies.Keywordsp73mutationmethylationhematologicalsystemLifeScienceResearch2009131091～094131Vol．13No．120092LifeScienceResearchFeb．2009··200979％DNA［3］.p73.TAp73△Np73P1TAtransactivationP2TA.△TAp73p73△ex2、p73△ex2/3、△N＇p733TAp73、［4］.TAp734N△Np73、p73△ex2、p73△ex2/3△N＇p73DNp73［3，4］dominantnegativep73.p73C9p73α、p73β、p73γ、p73δ、p73ε、p73ζ、p73η、p73η1、p73θ［3］..1.2p73p73、.TAp73p73.、DNATTAp73.3［5］1ScotinER2BaxPUMA3CD95.DNp73p73△Np73△TAp73.p53TAp73p53TAp73.p53TAp73.DNp73p53TAp73p53TAp73［6］.△Np73mRNABH3PUMA［7］.p53DNp73p53△Np73αNFκB［8］.p73.p73［1］.ZhangJ［9］△Np73TrKANGF.p73.2p732.1p73p53p73.p73.Sahu［10］PCR-SSCP120ALLacutelymphocyticleukemia14567p73mRNA.p73［3］.2.2p73.GalmO［11］AMLacutemyeliodleukemiap7313.3％.SchmelzK［12］DNA5--2′-5-Aza-2′-deoxycytidinep73p21AML.ALLp73.p73.PlutaA［3］ALLp73p73ALL18%～23%.Roman-Gomez［13］251ALLp73ALL.p73.Doorn［14］T-p7348％.SiuLL［15］NK921NHLp7394％p73.MMmultiplemyelomap73.GaimO［16］p73MM46％MM12.5％.13MMp73［17］.2.3p73AML、CML、ALLCLLp73p73［3］.TAp73△Np73［5］.△N/TAp73［5］.MMeier［18］T-ALLp73△TAp7388%TAp7312%.△TAp73△TAp73.p73△ex244％.T-ALL△TAp73T-ALLDNA.B-CLLB-CLLTAp73△Np7385％p73［19］.△Np73B-CLL.CarlosBueso-Ramos［20］p73p57kip2ALL.CD154CLL.CD154c-ablp73p53CLL［21］.3p73p730.5%［1］.p73.p73.p73AMLCML［3］.ALL、NHLp73p73.p73.p73p73.5--2′-AML［12］p73p73TAp73p73Ad-p73p73.△Np73.siRNA△Np73△Np73..p73、、.p73p73.（References）：[1]OZAKITNAKAGAWARAA.p73asophisticatedp53familymemberinthecancerworld[J].CancerSci20059611729-737.[2]VILGELMAEL-RIFAIWZAIKAA.Therapeuticprospectsforp73andp63Risingfromtheshadowofp53[J].DrugResistenceUpdates200811152-163.[3]PLUTAANYMANUJOSEPHBetal.Theroleofp73inhematologicalmalignancies[J].Leukemia200620757-766.[4]MARABESEMVIKHANSKAYAFBROGGINIM.p73Achiaroscurogeneincancer[J].EuropeanJournalofCancer2007431361-1372.[5]RAMADANSTERRINONIACATANIMVetal.p73inducesapoptosisbydifferentmechanisms[J].BiochemicalandBiophysicalResearchCommunications2005331713-717.[6]BUHLMANNSP譈TZERBM.DNp73amatterofcancerMechanismsandclinicalimplications[J].BiochimicaetBiophysicaActa20081785207-216.[7]SIM魻ES-W譈STAPSIGRISTBBELYANSKAYALetal.DeltaNp73antisenseactivatesPUMAandinducesapoptosisinneuroblastomacells[J].JournalofNeuro-oncology2005：p739320097229-34.[8]TANAKAYOTAKKAMEOKAMetal.Up-regulationofNFkappaB-responsivegeneexpressionbyDeltaNp73alphainp53nullcells[J].ExpCellRes20063121254-1264.[9]ZHANGJCHENX.DeltaNp73modulatesnervegrowthfactor-mediatedneuronaldifferentiationthroughrepressionofTrkA[J].MolCellBiol200727103868-3880.[10]SAHUGRDASBR.Alterationofp73inpediatricdenovoacutelymphoblasticleukemia[J].BiochemBiophysresComm-un2005327750-755.[11]GALMOWILOPSL譈DERCetal.ClinicalimplicationsofaberrantDNAmethylationpatternsinacutemyelogenousleukemia[J].AnnHematol20058439-46.[12]SCHMELZKWAGNERMD魻RKENBetal.5-Aza-2'-deoxycytidineinducep21MAFexpressbydemethylationofp73leadingtop53-independentapoptosisinmyeloidleukemia[J].IntJCancer20051145683-695.[13]JOSERGANTONIJVJUANA.Promoterhypermethylationofcancer-relatedgenesastrongindependentprognosticfactorinacutelymphoblasticleukemia[J].Blood20041042492-2498.[14]DOORNRVZOUTMANWHDIJKMANR.EpigeneticprofilingofcutaneousT-celllymphomapromoterhypermethy-lationofmultipletumorsuppressorgenesincludingBCL7aPTPRGandp73[J].JClinOncol200523173886-3896.[15]SIULLCHANJKWONGKFetal.Specificpatternsofgenemethylationinnaturalkillercelllymphomasp73isconsistentlyinvolved[J].AmJPathol2002160159-66.[16]GALMOWILOPSREICHELTJetal.DNAmethylationchangesinmultiplemyeloma[J].Leukemia2004181687-1692.[17]CHIMCSKWONGYLFUNGTKetal.Methylationprofilinginmultiplemyeloma[J].LeukRes200428379-385.[18]MEIERMDENBOERMLMEIJERINKJPPetal.Differentialexpressionofp73isoformsinrelationtodrugresistanceinchildhoodT-lineageacutelymphoblasticleukaemia[J].Leukemia2006201377-1384.[19]LEUPINNL譈THIIANOVAKUetal.p73statusinB-cellchroniclymphocyticleukemia[J].LeukLymphoma20044561205-1207.[20]BUESO-RAMOSCXUYMCDONNELLTJetal.Proteinexpressionofatriadoffrequentlymethylatedgenesp73p57Kip2andp15hasprognosticvalueinadultacutelymphocyticleukemiaindependentlyofitsmethylationstatus[J].ClinOncol200523173932-3939.[21]DICKERFKATERAPPRA