CTCFiscentraltosignalingpathwaysinimmatureBcellselicitedbycross-linkingtheIgBCRandstimulationwithTGF?.Bothstimuliresultininductionofcellcyclearrestandapoptosis.BCRligationstimulatesatransientinductionofMYCthatleadstohighlevelCTCFexpressionandfeedbacksuppressionofMYCtranscription.BCRligationalsoactivatesPTENopposingPI3KactivationofMYC.PharmacologicinactivationofPI3KormTOR/FRAPresultsinsuppressionofS6KresultinginactivationofCTCFandsuppressionofMYC.CTCFactivationinducestranscriptionalactivationofp19ARF,withitsdownstreamconsequences,andofp27.Growtharrestisoccasionedbyco-expressionofp21andp27andinhibitionofMYC.CTCF,isbonafide‘multivalent’DNA-sequencebinderwhichspecificityismediatedbydifferentsetsofzincfingers(ZFs).ForthreedifferentDNAtargetsites,particulargroupsofZFswhichcannotbedeletedfromthe11ZFdomainwithoutloosingbindingtoagivensite,areshownbya‘rainbow’intheboxontheleft. Contributor:KosiGramatikoff,PhD REFERENCES:ElenaM.etal.LobanenkovFunctionalPhosphorylationSitesintheC-TerminalRegionoftheMultivalentMultifunctionalTranscriptionalFactorCTCFMol.Cell.Biol.,Mar2001;21:2221-2234.EMKlenovaetal.MolecularweightabnormalitiesoftheCTCFtranscriptionfactor:CTCFmigrates...NucleicAcidsRes.,Feb1997;25:466-474.GNFilippovaetal.Anexceptionallyconservedtranscriptionalrepressor,CTCF,employsdifferentcombinationsofzincfingerstobinddivergedpromotersequencesofavianandmammalianc-myconcogenesMol.Cell.Biol.,Jun1996;16:2802-2813.IgorV.etal.PhysicalandFunctionalInteractionbetweenTwoPluripotentProteins,theY-boxDNA/RNA-bindingFactor,YB-1,andtheMultivalentZincFingerFactor,CTCFJ.Biol.Chem.,Sep2000;275:29915-29921.JohnE.J.Raskoetal.CellGrowthInhibitionbytheMultifunctionalMultivalentZinc-FingerFactorCTCFCancerRes.,Aug2001;61:6002-6007.