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1、ANTIOXIDANTS&REDOXSIGNALINGCOMPREHENSIVEINVITEDREVIEWVolume12,Number6,2010ªMaryAnnLiebert,Inc.DOI:10.1089=ars.2009.2609NuclearRedoxSignalingMargareteLukosz,SaschaJakob,NicoleBu¨chner,Tim-ChristianZschauer,JoachimAltschmied,andJudithHaendelerAbstractReactiveoxygenspecieshavebeendescribedtomodulatep
2、roteinswithinthecell,aprocesscalledredoxregulation.However,theimportanceofcompartment-specificredoxregulationhasbeenneglectedforalongtime.Intheearly1980sand1990s,manyinvitrostudiesintroducedthepossibilitythatnuclearredoxsignalingexists.However,thefunctionalrelevanceforthathasbeengreatlydisregarded.
3、Recently,ithasbecomeevidentthatnuclearredoxsignalingisindeedoneimportantsignalingmechanismregulatingavarietyofcellularfunctions.Transcriptionfactors,andevenkinasesandphosphatases,havebeendescribedtoberedoxregulatedinthenucleus.Thisreviewdescribesseveraloftheseproteinsincloserdetailandexplainstheir
4、functionsresultingfromnuclearlocalizationandredoxregulation.Moreover,theredoxstateofthenucleusandseveralimportantnuclearredoxregulators[Thioredoxin-1(Trx-1),Glutaredoxins(Grxs),Peroxiredoxins(Prxs),andAPEXnuclease(multifunctionalDNA-repairenzyme)1(APEX1)]areintroducedmoreprecisely,andtheirnecessit
5、yforregulationoftranscriptionfactorsisemphasized.Antioxid.RedoxSignal.12,713–742.I.Introduction714II.NuclearRedoxRegulators714A.Redoxstateofthenucleus714B.Antioxidativeenzymesinthenucleus716C.Thioredoxin-1(Trx-1)716D.Glutaredoxins(Grxs)andperoxiredoxins(Prxs)717E.APEXnuclease(multifunctionalDNA-re
6、pairenzyme)1(APEX1)717F.Trx-1=APEX1interactions718III.Redox-RegulatedTranscriptionFactorsandChromatinModifiers720A.Activatorprotein-1(AP-1)720B.CyclicAMPresponseelement–bindingprotein(CREB)720C.Specificityprotein1(Sp1)720D.Nuclearreceptors721E.Nuclearfactor-kappaB(NF-kB)721F.p53722G.NuclearfactorI=C
7、AATtranscriptionfactor(NFI=CTF)723H.Hypoxia-induciblefactor1(HIF-1)723I.Nuclearfactorerythroid2–relatedfactor2=NF-E2relatedfactor2(Nrf-2)724J.HomeoboxB5(HoxB5)725K.Otherredox-regulatedtranscriptionfactors725L.His
