Thetubbygeneproductisexpressedinthebrainandhasbeenimplicatedbymousegeneticsinobesityandotherdisorderssuchasblindness.Structuralanalysispredictedthatthisgeneactsasatranscriptionfactor,bindingtoDNAtoregulategeneexpression.Morerecently,itwasreportedthattubbybindstophosphoinositidesintheplasmamembrane,helpingtolocalizethisfactorinthemembraneregionintheabsenceofpathwayactivation.TubbyalsointeractswithGalpha-qg-proteinsubunits,localizingtubbytoregionsofg-proteinactivation.ActivationofphosphipaseCactivityandhydrolysisofmembranephosphoinositidesleadstoreleaseoftubbyfromtheplasmamembrane,allowingtubbytoenterthenucleustobindDNAandregulatetranscription.SomeG-proteincoupledreceptorssuchas5-HT2cmaysignalinpartthroughtubbyinadditiontocalcium-mediatedpathwaysandprotein-kinasesignalingpathways.Theidentityofgenesregulatedbytubbyandthemechanismbywhichtubbyaffectsobesityremaintobeexplored.

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REFERENCES:Boggon,T.J.,Shan,W.S.,Santagata,S.,Myers,S.C.,andShapiro,L.(1999)Implicationoftubbyproteinsastranscriptionfactorsbystructure-basedfunctionalanalysis.Science286(5447):2119-2125Santagata,S.,Boggon,T.J.,Baird,C.L.,Gomez,C.A.,Zhao,J.,Shan,W.S.,Myszka,D.G.,andShapiro,L.(2001)G-ProteinSignalingThroughTubbyProteins.Science292(5524):2041-2050