Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells 英文参考文献.docVIP

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Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells 英文参考文献.doc

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Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells 英文参考文献

SilencingNuclearPoreProteinTprElicitsaSenescent- LikePhenotypeinCancerCells BrigitteDavid-Watine* InstitutPasteur,CNRSURA2582,GroupeE3BiologieCellulaireduNoyau,Paris,France Abstract Background:Tprisalargecoiled-coilproteinlocatedinthenuclearbasketofthenuclearporecomplexforwhichmany differentfunctionswereproposedfromyeasttohuman. Methodology/Principal Findings: Here we show that depletion of Tpr by RNA interference triggers G0–G1 arrest and ultimatelyinducesasenescent-likephenotypedependentonthepresenceofp53.WealsofoundthatTprdepletionimpairs the NES [nuclear export sequence]-dependent nuclear export of proteins and causes partial co-depletion of Nup153. In additionTprdepletionimpactsonlevelandfunctionoftheSUMO-proteaseSENP2thusaffectingSUMOylationregulationat thenuclearporeandoverallSUMOylationinthecell. Conclusions:Ourdataforthefirsttimeprovideevidencethatanuclearporecomponentplaysaroleincontrollingcellular senescence.OurfindingsalsopointtonewrolesforTprintheregulationofSUMO-1conjugationatthenuclearporeand directlyconfirmTprinvolvementinthenuclearexportofNES-proteins. Citation: David-Watine B (2011) Silencing Nuclear Pore Protein Tpr Elicits a Senescent-Like Phenotype in Cancer Cells. PLoS ONE 6(7): e22423. doi:10.1371/ journal.pone.0022423 Editor:MichaelPolymenis,TexasAMUniversity,UnitedStatesofAmerica ReceivedApril1,2011;AcceptedJune22,2011;PublishedJuly19,2011 Copyright:?2011 BrigitteDavid-Watine.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was supported by the Institut Pasteur. The funders had no role in study design, data collection and analysis, decision to publish, or preparationofthemanuscript. CompetingInterests:Theauthorhasdeclaredthatnocompetinginterestsexist. *E-mail:brigitte.david-watine@pasteur.fr Introduction thaliana between ESD4 and NUA, which are homologues of Ulp1pandT