Role of the HCF-1 Basic Region in Sustaining Cell Proliferation 英文参考文献.docVIP

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Role of the HCF-1 Basic Region in Sustaining Cell Proliferation 英文参考文献.doc

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Role of the HCF-1 Basic Region in Sustaining Cell Proliferation 英文参考文献

RoleoftheHCF-1BasicRegioninSustainingCell Proliferation MarcoMangone¤a,MichaelP.Myers¤b,WinshipHerr*¤c WatsonSchoolofBiologicalSciences,ColdSpringHarborLaboratory,ColdSpringHarbor,NewYork,UnitedStatesofAmerica Abstract Background:Thehumanherpessimplexvirus-associatedhostcellfactor1(HCF-1)isaconservedhumantranscriptionalco- regulator that links positive and negative histone modifying activities with sequence-specific DNA-binding transcription factors.Itissynthesizedasa2035aminoacidprecursorthatiscleavedtogenerateanamino-(HCF-1N)terminalsubunit, whichpromotesG1-to-Sphaseprogression,andacarboxy-(HCF-1C)terminalsubunit,whichcontrolsmultipleaspectsof celldivisionduringMphase.TheHCF-1NsubunitcontainsaKelchdomainthattethersHCF-1tosequence-specificDNA- bindingtranscriptionfactors,andapoorlycharacterizedsocalled‘‘Basic’’region(owingtoahighratioofbasicvs.acidic amino acids) that is required for cell proliferation and has been shown to associate with the Sin3 histone deacetylase (HDAC)component.HerewestudiedtheroleoftheBasicregionincellproliferationandG1-to-Sphasetransitionassays. Methodology/PrincipalFindings:Surprisingly,muchlikethetranscriptionalactivationdomainsofsequence-specificDNA- bindingtranscriptionfactors,thereisnouniquesequencewithintheBasicregionrequiredforpromotingcellproliferation orG1-to-Sphasetransition.Indeed,theabilitytopromotetheseactivitiesissizedependentsuchthattheshortertheBasic region segment the less activity observed. We find, however, that the Basic region requirements for promoting cell proliferationinatemperature-sensitivetsBN67cellassayaremorestringentthanforG1-to-SphaseprogressioninanHCF-1 siRNA-depletionHeLa-cellassay.Thus,eitherhalfoftheBasicregionalonecansupportG1-to-Sphaseprogressionbutnot cellproliferationeffectivelyintheseassays.Nevertheless,theBasicregiondisplaysconsiderablestructuralplasticitybecause eachhalfisabletopromotecellproliferationwhenduplicatedintandem.Consistentwithapotentialroleinpromotingcell- cycleprogression,theSin3aHDACc