Likeubiquitin,SUMO(smallubiquitin-relatedmodifier)proteinsaresmallproteintagsthatareconjugatedtoproteinstomodifytheirfunction.Theubiquitinsystemtagsproteinsfordegradationbytheproteosome(seeProteosomepathway)butSUMOconjugationhasarangeofotherfunctions,stABIlizingsomeproteinsandalteringtheirsubcellularlocalization.Sumoylationmayalsoinfluenceubiquitinationandproteinstabilityindirectly.ThreedifferentSUMOproteinsareconjugatedtoproteins,SUMO-1,SUMO-2andSUMO-3.TheSUMO-2andSUMO-3genesarecloselyrelated,with86%sequenceidentitywhileSUMO-1islesscloselyrelatedwithabout50%sequenceidentitywithSUMO-2andSUMO-3.TheseSUMOproteinsalsohavedistinctfunctions,withSUMO-1conjugatedtoproteinsasamonomer,whileSUMO-2andSUMO-3areconjugatedtoproteinsashighermolecularweightpolymerswithSUMO-1terminatingfurtherSUMOaddition.SUMOproteinsarefirstactivatedbyadenylationbyoneenzymecomplex(SAE1/SAE2),thentransferredtoUbc-9andfinallytotheterminalaminogroupofalysinesidechainintargetproteins.ThesameconjugationsystemappearstoworkforallthreeSUMOproteins.OnetargetofSUMOmodificationisproteinsinvolvedinformationofthePMLnuclearbodies,promotingthestabilityofthesestructuresandperhapsalteringtheirroleintranscriptionalregulation,cellularproliferationandanti-viralresponses.OthertargetsofSUMOadditionincludeDAXX,p53andran-Gap.Thetranscriptionalactivationbyp53isincreasedbySUMOaddition.ThelocalizationofDAXXtothePMLnuclearbodiesandthelocalizationofran-GaptothenuclearporesarealsoregulatedbySUMOaddition.Theactivityofseveraltranscriptionfactorsisalteredbysumoylation,includingC/EBPproteins,c-Myb,glucocorticoidreceptor,androgenreceptor,andprogesteronereceptor.PIASisaproteinthatmodulatestheactivityofmanydifferenttranscriptionfactorsperhapsbyactingitselfasasumoligase.SumoylationoftopoisomeraseIaltersitslocalizationinthenucleus,andhistonedeacetylaseenzymesaretargetsofthissystem.Viralproteinsaretargetsofsumoylation,suggestingthatinfectionandanti-viralcellulardefensesmaybeaffectedbythissystem.Sumoylationmayalsoalterthestabilityofproteinswithpolyglutaminerepeatsinvolvedinneurodegenerativedisorders,addingfurthertotheimportantanddiverserolesofthisproteinmodificationsystem.

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REFERENCES:TathamMH,TheJournalofBIOLOGicalChemistry(2001)276(38):35368-35374.PolymericChainsofSUMO-2andSUMO-3areConjugatedtoProteinSubstratesbySAE1/SAE2andUbc9.

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