Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells 英文参考文献.docVIP
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Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells 英文参考文献
NuclearEntryofActivatedMAPKIsRestrictedinPrimary
OvarianandMammaryEpithelialCells
ElizabethR.Smith1,2*,KathyQiCai3,JenniferL.Smedberg3,MelinaM.Ribeiro1,2,MalgorzataE.Rula3,
CarolynSlater3,AndrewK.Godwin3,Xiang-XiXu1,2
1DepartmentofMedicine,UniversityofMiamiMillerSchoolofMedicine,Miami,Florida,UnitedStatesofAmerica,2SylvesterComprehensiveCancerCenter,Universityof
MiamiMillerSchoolofMedicine,Miami,Florida,UnitedStatesofAmerica, 3OvarianCancerandTumorCellBiologyPrograms, DepartmentofMedicalOncology,Fox
ChaseCancerCenter,Philadelphia,Pennsylvania,UnitedStatesofAmerica
Abstract
Background: The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway.
PhosphorylationbyMEKactivatesMAPK/ERKinthecytoplasm,andphospho-ERKisthoughttoenterthenucleusreadily
tomodulatetranscription.
Principal Findings: Here, however, we observe that in primary cultures of breast and ovarian epithelial cells,
phosphorylationandactivationofERK1/2aredisassociatedfromnucleartranslocalizationandtranscriptionofdownstream
targets,suchasc-Fos,suggestingthatnucleartranslocationislimitedinprimarycells.Accordingly,inimportassaysinvitro,
primarycellsshowedalowerimportactivityforERK1/2thancancercells,inwhichactivatedMAPKreadilytranslocatedinto
the nucleus andactivated c-Fos expression. Primary cells express lower levels of nuclear porecomplex proteins and the
nucleartransportfactors,importinB1andimportin7,whichmayexplainthelimitingERK1/2importfoundinprimarycells.
Additionally,reductioninexpressionofnucleoporin153bysiRNAtargetingreducedERK1/2nuclearactivityincancercells.
Conclusion:ERK1/2activationisdissociatedfromnuclearentry,whichisaratelimitingstepinprimarycellsandinvivo,and
therestrictionofnuclearentryisdisruptedintransformedcellsbytheincreasedexpressionofnuclearporesand/ornuclear
transportfactors.
Citation: SmithER, CaiKQ,SmedbergJL,RibeiroMM,RulaME,etal.(2010)NuclearEntryofActivatedMAPKIsRestricted inPrimaryOvarianandMammary
EpithelialCells.PLoSONE5(2
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