Themoleculareventsthatleadtotheperceptionofpainareakeyresearchfieldinmedicineanddrugdiscovery.Theopioidreceptorsmodulatepainsignalinginresponsetoendogenouspeptideligandsandopiatedrugssuchasmorphine.Thekappaopioidreceptorplaysakeyroleintheprofoundanalgesiaofopiatesandisactivatedbytheendogenouspeptideliganddynorphin,encodedbytheprodynorphingene.Productionofprodynorphinistranscriptionallyregulatedbyadownstreamregulatoryelement(DRE)intheprodynorphingene.AtranscriptionfactorcalledDREAM(DREantagoNISTicmodulator)bindstotheDREandrepressesprodynorphintranscriptionwhenbound.DREAMbindscalciumwith4EF-handmotifsandthebindingofDREAMtoDNAisrepressedinthepresenceofcalcium.Manytranscriptionfactorsareregulatedbycalciumindirectlythroughcalciumsensitivekinasesandphosphatases,butDREAMisuniquetodateinbeingatranscriptionfactorthatdirectlybindscalciumandisregulatedbycalciumbinding.DREAMmayalsoregulateothergenessuchasc-fos.DREAMisexpressedinspinalcordneuronsinregionsinvolvedinpainsignaling.TheregulationofprodynorphinexpressionbyDREAMalsoleadstothehypothesisthatDREAMisinvolvedinpainsignaling.TransgenicmicelackingtheDREAMgenewereunusuallypaininsensitiveandhadelevatedspinallevelsofdynorphinandtonicactivationofthekappaopioidreceptor,supportingthishypothesis.OtherfunctionsofDREAMmayexistsuchasregulationofpresenilinsandpotassiumchannelactivityintheheart.DREAMisalsoknownascalsenilinandKChIP3throughitsassociationwiththeseotherproteins.TheseprocesseswerenotaffectedinmicelackingtheDREAMgenehowever.

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REFERENCES:Carrion,A.M.etal.(1999)DREAMisaCa2+-regulatedtranscriptionalrepressor.Nature398(6722),80-4Cheng,H.Y.etal.(2002)DREAMIsaCriticalTranscriptionalRepressorforPainModulation.Cell108(1),31-43Osawa,M.etal.(2001)Calcium-regulatedDNAbindingandoligomerizationoftheneuronalcalcium-sensingprotein,calsenilin/DREAM/KChIP3.J.Biol.Chem.276(44),41005-13

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