ContentslistsavailableatScienceDirectSeminarsinCell&DevelopmentalBiologyjournalhomepage:www.elsevier.com/locate/semcdbReviewRolesofubiquitininautophagyandcelldeathCarlosGómez-Díaz,FumiyoIkeda⁎InstituteofMolecularBiotechnologyofAustrianAcademyofSciences(IMBA),ViennaBiocenter,Dr.Bohr-gasse3,Vienna,AustriaARTICLEINFOKeywords:AutophagyCelldeathDeubiquitinaseE3ligaseInflammationUbiquitinABSTRACTThebalancebetweencellsurvivalandcelldeathisoftenlostinhumanpathologiessuchasinflammationandcancer.Autophagyplaysacriticalroleincellsurvival:essentialnutrientsaregeneratedbyautophagy-dependentdegradationandrecyclingofcellulargarbage.Ontheotherhand,celldeathisinducedbydifferentprograms,suchasapoptosis,pyroptosis,andnecroptosis.Emergingevidenceisrevealinghowcellsurvivalandcelldeathpathwaysarecoordinatedtodeterminecellfate.Forinstance,posttranslationalmodificationofproteinswithubiquitinregulatesmanystepsofautophagyandcelldeathpathways.Inthisreviewarticle,wewilldiscusshowtheubiquitinsysteminfluencescelldeathandautophagy.1.IntroductionTheregulationofcellfatebyopposingcelldeathandcellsurvivalpathwaysisimportantforcellularandtissuehomeostasis[1].Dysre-gulationofthesesignalingpathwayscaninducepathologicalconditionssuchasinflammatoryandneuronaldiseases[2].Theubiquitinationsystemplayscriticalrolesinthepathwaysforcellsurvival(e.g.au-tophagy)andcelldeath(e.g.apoptosis,necroptosis)[3–5].Further-more,autophagyandcelldeathpathwaysexhibitextensivecrosstalk[6,7].Thislinkisespeciallywell-understoodinDrosophila[8].Forex-ample,programmedcelldeathintheDrosophilalarvalmidguttissueisdependentonautophagy,andsomeautophagy-related(ATG)genesareinvolvedinthisprocess[9].Inmammals,autophagy-dependentcelldeathislimitedandoccursinacontext-dependentmanner[10,11].Interestingly,regulatorsoftheubiquitinsystemplayaroleinbothcelldeathandautophagyinmammals,whichwewilldiscussinthisreview.The76aminoacidproteinubiquitinisexpressedinallcelltypesandplaysafundamentalroleinbiology[12].Amajorfunctionofubiquitinistoposttr...
