ContentslistsavailableatScienceDirectMolecularAspectsofMedicinejournalhomepage:www.elsevier.com/locate/mamControlofSUMOandUbiquitinbyROS:SignalinganddiseaseimplicationsNicolasStankovic-Valentin∗,FraukeMelchior∗∗ZentrumfürMolekulareBiologiederUniversitätHeidelberg(ZMBH),DKFZ-ZMBHAlliance,Heidelberg,GermanyARTICLEINFOKeywords:UbiquitinSUMORedoxsignalingOxidativestressCysteineoxidationNADPHoxidaseABSTRACTReversiblepost-translationalmodifications(PTMs)ensurerapidsignaltransmissionfromsensorstoeffectors.ReversiblemodificationofproteinsbythesmallproteinsUbiquitinandSUMOareinvolvedinvirtuallyallcellularprocessesandcanmodifythousandsofproteins.UbiquitinationorSUMOylationisthereversibleat-tachmentofthesemodifierstolysineresiduesofatargetviaisopeptidebondformation.ThesemodificationsrequireATPandanenzymaticcascadecomposedofthreeclassesofproteins:E1activatingenzymes,E2con-jugatingenzymesandE3ligases.Thereversibilityofthemodificationisensuredbyspecificisopeptidases.E1andE2enzymes,someE3ligasesandmostisopeptidaseshavecatalyticcysteineresidues,whichmakethempotentiallysusceptibleforoxidation.Indeed,anincreasingnumberofexamplesrevealregulationofubiquiti-nationandSUMOylationbyreactiveoxygenspecies,bothinthecontextofredoxsignalingandinsevereoxi-dativestress.Importantly,ubiquitinationandSUMOylationplayessentialrolesintheregulationofROShomeostasis,participatinginthecontrolofROSproductionandclearance.Inthisreview,wewilldiscusstheinterplaybetweenROShomeostasis,UbiquitinandSUMOpathwaysandtheimplicationsfortheoxidativestressresponseandcellsignaling.1.IntroductionAmajorchallengeinbiologyistounderstandhowcellssensetheirenvironment,integratemultipleinformation,transmitit,andmaketheappropriatedecision.Signaltransductionistheprocessbywhichasignalistransmittedfromthesensortotheeffector.Thisisensuredbyseveralmechanisms,includingforexampleallostericregulationofen-zymesbyCa2+orpost-translationalmodifications(PTM)ofproteins(Deribeetal.,2010).PTMsthatarereversiblemodificationscanactasmolecular...
