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1、TheUbiquitin-ProteasomeSystemandItsRoleinInflammatoryandAutoimmuneDiseasesCellular&MolecularImmunologylview255TheUbiquitin-ProteasomeSystemandItsRoleinInflammatoryandAutoimmuneDiseasesJingsongWang,vandMichaelA.MaldonadoProteindegradationthroughtheubiquitin?-proteasomesystemisthemajorpathway
2、ofnon?-lysosomalproteolysisofintracellularproteins.Itplaysimportantrolesinavarietyoffundamentalcellularprocessessuchasregulationofcellcycleprogression,division,developmentanddifferentiation,apoptosis,celltrafficking,andmodulationoftheimmuneandinflammatoryresponses.Thecentralelementofthissystemi
3、sthecovalentlinkageofubiquitintotargetedproteins,whichalethenrecognizedbythe26Sproteasome,anadenosinetriphosphate-dependent,multi-catalyticprotease.Damaged,oxidized,ormisfoldedproteinsaswellasregulatoryproteinsthatcontrolmanycriticalcellularfunctionsareamongthetargetsofthisdegradationprocess.Ab
4、errationofthissystemleadstothedysregulationofcellularhomeostasisandthedevelopmentofmultiplediseases.Inthisreview,wedescribedthebasicbiochemistryandmolecularbiologyoftheubiquitin-proteasomesystem,anditscomplexroleinthedevelopmentofinflammatoryandantoimmunediseases.Inaddition.therapiesandpotentia
5、ltherapeutictargetsrelatedtotheubiquitin-proteasomesystemarediscussedaswel1.Ce//ular&MolecularImmunology.2006;3(4):255.261.ubiquitin,proteasome,proteindegradation,inflammation,autoimmunediseaseIntroductionThe2004NobelPrizeinChemistrywasawardedtoagroupofscientistsforthediscoveryofthefunction
6、ofubiquitinn.41.Ubiquitinispartoftheubiquitin-proteasomesystem(UPS1matisresponsibleforthedegradationofmorethan80%ofnormalandabnormalintracellularproteins.Attheheartofmissystemisthe26Sproteasome.adynamicmultisubunitproteolyticcomplexwithamolecularweightof700kDthat.ineukaryotes,functionsasthekeye
7、nzymefornon.1ysosomalproteindegradation.Proteasomaldegradationremovesdenatured,misfolded,damagedorimproperlytranslatedproteinsfromcellsandaswellasregulatingthelevelofproteinssuchascyclinsandtranscriptionfactors.Theproductsresultin
