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

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