Cellular Contractility Requires Ubiquitin Mediated Proteolysis 英文参考文献.docVIP

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Cellular Contractility Requires Ubiquitin Mediated Proteolysis 英文参考文献.doc

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Cellular Contractility Requires Ubiquitin Mediated Proteolysis 英文参考文献

CellularContractilityRequiresUbiquitinMediated Proteolysis YuvalCinnamon1,OrenFeine1,HelfridHochegger2,AlexanderBershadsky3,MichaelBrandeis1* 1TheDepartmentofGenetics,TheSilbermanInstituteofLifeSciences,TheHebrewUniversityofJerusalem,GivatRam,Jerusalem,Israel,2SussexCentreforGenome DamageandStability,UniversityofSussex,Brighton,UnitedKingdom,3DepartmentofMolecularCellBiology,TheWeizmannInstituteofScience,Rehovot,Israel Abstract Background: Cellularcontractility, essentialforcellmovementandproliferation,isregulatedbymicrotubules, RhoAand actomyosin.TheRhoAdependentkinaseROCKensuresthephosphorylationoftheregulatoryMyosinIILightChain(MLC) Ser19, thereby activating actomyosin contractions. Microtubules are upstream inhibitors of contractility and their depolymerization or depletion cause cells to contract by activating RhoA. How microtubule dynamics regulates RhoA remains,amajormissinglinkinunderstandingcontractility. PrincipalFindings:Weobservedthatcontractilityisinhibitedbymicrotubulesnotonly,aspreviouslyreported,inadherent cells, but also in non-adhering interphase and mitotic cells. Strikingly we observed that contractility requires ubiquitin mediatedproteolysisbyaCullin-RINGubiquitinligase.Inhibitionofproteolysis,ubiquitinationandneddylationallledto completecessationofcontractilityandconsiderablyreducedMLCSer19phosphorylation. Conclusions:Ourresultsimplythatcellsexpressacontractilityinhibitorthatisdegradedbyubiquitinmediatedproteolysis, eitherconstitutivelyorinresponsetomicrotubuledepolymerization.ThisdegradationseemstodependonaCullin-RING ubiquitinligaseandisrequiredforcellularcontractions. Citation: CinnamonY, Feine O,Hochegger H,BershadskyA,BrandeisM(2009) Cellular Contractility Requires UbiquitinMediated Proteolysis. PLoS ONE 4(7): e6155.doi:10.1371/journal.pone.0006155 Editor:NeilHotchin,UniversityofBirmingham,UnitedKingdom ReceivedMarch10,2009;AcceptedJune6,2009;PublishedJuly14,2009 Copyright: ?2009 Cinnamon et al. This is an open-access article dis