Ubiquitin-ligases-mediate-growth-and-development

UbiquitinligasesmediategrowthanddevelopmentbypromotingproteindeathSophiaLStone1andJudyCallis2Theubiquitinproteasomesystem(UPS)allowsplantstoeffectivelyandefficientlyaltertheirproteomesoastoensuredevelopmentalplasticityandenvironmentaladaptation.RecentworkhasdemonstratedthattheUPSisanintegralpartofmultiplehormone-signalingpathways,whichmodulatecellgrowthanddifferentiation.Inresponsetovariationinhormonelevels,theUPSregulatestheabundanceofsignalingfactors,mainlyhormone-responsivetranscriptionfactors,whichmediatecellularresponses.RecentexcitingstudieshaveshownthathormonesdirectlyorindirectlymodulatesubstrateubiquitinationbyregulatingE3-substrateinteraction.OtheravenuesofregulationincluderegulatingE3mRNAabundance.Addresses1DepartmentofBiology,DalhousieUniversity,1355OxfordSt.,Halifax,NSB3H4J1,Canada2SectionofMolecularandCellularBiology,CollegeofBiologicalSciences,UniversityofCalifornia-Davis,OneShieldsAve.,Davis,CA95616,USACorrespondingauthor:Callis,Judy([e-mail])CurrentOpinioninPlantBiology2007,10:624–632ThisreviewcomesfromathemedissueonCellBiologyEditedbyBenScheresandVolkerLipkaAvailableonline11thSeptember20071369-5266/$–seefrontmatter#2007ElsevierLtd.Allrightsreserved.DOI10.1016/j.pbi.2007.07.010IntroductionAplant’sabilitytoaltergrowthanddevelopmentreliesheavilyonproteomicplasticity.Regulatedubiquitin-mediatedandproteasome-mediateddegradation,there-fore,playsacrucialroleinenablingplantstoaltertheirproteomeinordertodifferentiateintotheappropriatecell,tissueand/ororgantypeandtomaximizetheirchancesofsurvivalindifferentenvironments.Toaccom-plishthis,hormonesactasimportantintegratorsofendogenousandexogenoussignals.Geneticapproachestoelucidatethemolecularmechan-ismsofhormoneactionhaverevealeddirectlinksbetweenhormoneproduction,perception,signaltransductionandoutputsandtheubiquitinproteasomesystem(UPS).Ubi-quitin-mediateddegradationofproteinsintheperceptionof,and/orresponseto,hormonalstimuliisatthecoreofmanyhormone-signalingpathways.WithseveralrecentexcitingadvancesinunderstandingUPS-mediatedregulationofhormonesignaling,thisreviewwillfocusmainlyonnewdiscoveriesinthepastfewyearsonE3ligasesimplicatedinhormonalresponses.E3componentsimplicatedindevelopmentalprocessesbutnotlinkedtoaspecifichormonalpathwayarelistedinTable1,whilethoselinkedtoaspecificpathwayarelistedinTable2.ThereaderisreferredtoseveralrecentreviewsfordiscussionoftheroleoftheUPSinphotomorphogenesis[1]andbioticstress[2,3].UbiquitinE3ligasesTheUPSpathwayincludestheE1(ubiquitinactivating),E2(ubiquitinconjugating)andE3(ubiquitinligase)enzymesrequiredforcovalentattachmentofthe76-aaproteinubiquitintoasubstrateprotein,aswellastheproteinsinvolvedinrecognition,transportandcatabolismoftheubiquitinatedsubstrate(Figure1).Forseveralreasons,ubiquitinisaversatilepost-translationalmodi-fication.First,asingleubiquitinhasmultipleprotein-interactionsurfaces.Second,one,afewormanyubiquitinmoietiescanbeattachedatoneormoresubstrateresi-dues.Finally,ubiquitin–ubiquitinlinkagesofanattachedubiquitinchaincanoccurviaone(orpossiblymorethanone)ofsevenubiquitinlysylresidues,producingstruc-turallydiverseubiquitinchains[4].Thesedifferentformsofattachedubiquitincanberecognizedbydistinctdown-streamcomponents[5].Thebestcharacterizedfunctionforubiquitinationisproteasome-catalyzedhydrolysisofproteinsmodifiedwithalysine-48(K48)-linkedpolyubi-quitinchain.However,anumberofnon-proteasomalfunctions,includingreceptorendocytosis,proteinacti-vationandproteinsortinghavealsobeenlinkedtoubiquitination,typicallyutilizingmonoubiquitinornon-K48ubiquitin–ubiquitinlinkages[6].Substratespecificityislargelygovernedbythesubstrate-recruitingE3ligases,whichgroupintothreeclassesonthebasisoftheE2-interactingregion,eitheraHomologytoE6-AssociatedCarboxy-Terminus(HECT),U-boxorReallyInterestingNewGene(RING)domain(Figure1).UnlikeallotherE3sthatnon-covalentlyfacilitateubi-quitintransferfromtheE2-ubiquitinintermediatetothesubstrate,HECTdomainproteinsformacovalentthioester-linkedE3-ubiquitinintermediatebeforesub-strateubiquitination(Figure1).ThenumberofE3ligasesencodedinonegenomeislarge.Forexample,theArabidopsisgenomeispredictedtoencodefor7HECT-type,61U-box-typeand475RING-typeE3ligaseproteinsthatfunctionasmonomericE3s,orascomponentsofmulti-subunitE3ligases[7].MonomericE3ligasescontainthesubstrate-bindingandE2-bindingCurrentOpinioninPlantBiology2007,10:624–632(APC)andcullin-RINGligases(CRLs),havethesedomainsonseparateproteins.Exchangeablesubunitsinmulti-subunitE3sprovideforanevengreaternumberofuniqueE3s,whichisespeciallytrueforCRLs.ThreetypesofCRLshavebeendescribedinplants,eachwithadifferentcullinsubunit(CUL1,CUL3a/3borCUL4).Thecullinproteinformsthescaffold,bindingtheinvariantRINGproteinatitsC-terminusandasubstrate-recognitionmoduleattheN-terminus[8].Forexample,thesubstrate-recognitionmoduleforCullin1-basedCRLsisArabidopsisSuppressorofKinetochoreProtein1(ASK)andthesubstrate-recruitingF-boxprotein,ofwhichthereareover700p