Cbl-c Ubiquitin Ligase Activity Is Increased via the Interaction of Its RING Finger Domain with a LIM Domain of the Paxillin Homolog, Hic 5 英文参考文献.docVIP

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Cbl-c Ubiquitin Ligase Activity Is Increased via the Interaction of Its RING Finger Domain with a LIM Domain of the Paxillin Homolog, Hic 5 英文参考文献.doc

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Cbl-c Ubiquitin Ligase Activity Is Increased via the Interaction of Its RING Finger Domain with a LIM Domain of the Paxillin Homolog, Hic 5 英文参考文献

Cbl-cUbiquitinLigaseActivityIsIncreasedviathe InteractionofItsRINGFingerDomainwithaLIMDomain ofthePaxillinHomolog,Hic5 PhilipE.Ryan1,2,StephenC.Kales1,RajgopalYadavalli1,MarionM.Nau1,HanZhang1, StanleyLipkowitz1* 1LaboratoryofCellularandMolecularBiology,CenterforCancerResearch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesof America,2TheGeorgeWashingtonUniversity,InstituteforBiomedicalSciences,Washington,DistrictofColumbia,UnitedStatesofAmerica Abstract Cblproteins(Cbl,Cbl-bandCbl-c)areubiquitinligasesthatarecriticalregulatorsoftyrosinekinasesignaling.Inthisstudy we identify a new Cbl-c interacting protein, Hydrogen peroxide Induced Construct 5 (Hic-5). The two proteins interact throughanovelinteractionmediatedbytheRINGfingerofCbl-candtheLIM2domainofHic-5.Further,thisinteractionis mediatedanddependentonspecificzinccoordinatingcomplexeswithintheRINGfingerandLIMdomain.BindingofHic-5 toCbl-cleadstoanincreaseintheubiquitinligaseactivityofCbl-conceCbl-chasbeenactivatedbySrcphosphorylationor throughanactivatingphosphomimeticmutation.Inaddition,co-transfectionofHic-5withCbl-cleadstoanincreaseinCbl- cmediatedubiquitinationoftheEGFR.ThesedatasuggestthatHic-5enhancesCbl-cubiquitinligaseactivityonceCbl-chas beenphosphorylatedandactivated.InteractionsbetweenheterologousRINGfingershavebeenshowntoactivateE3s.This is the first demonstration of enhancement of ubiquitin ligase activity of a RING finger ubiquitin ligase by the direct interactionofaLIMzinccoordinatingdomain. Citation:RyanPE,KalesSC,YadavalliR,NauMM,ZhangH,etal.(2012)Cbl-cUbiquitinLigaseActivityIsIncreasedviatheInteractionofItsRINGFingerDomain withaLIMDomainofthePaxillinHomolog,Hic5.PLoSONE7(11):e49428.doi:10.1371/journal.pone.0049428 Editor:MichaelMassiah,GeorgeWashingtonUniversity,UnitedStatesofAmerica ReceivedSeptember5,2012;AcceptedOctober8,2012;PublishedNovember7,2012 Thisisanopen-accessarticle,freeofallcopyright,andmaybefreelyreproduced,distributed,transmitted,modified,builtup