INVESTIGADORES
BLAUSTEIN KAPPELMACHER Matias
congresos y reuniones científicas
Título:
Regulation of Akt activity by SUMO conjugation
Autor/es:
MATÍAS BLAUSTEIN
Lugar:
Mendoza
Reunión:
Congreso; XLIX Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2013
Institución organizadora:
SAIB
Resumen:
Ourlaboratorystudiestheregulationofpre-mRNAalternativesplicingbysignaltransductionpathways.WehavereportedthatAktactivationregulatestheactivityoftwosplicingfactorsoftheSRproteinfamily(SRSF1andSRSF7),alteringdifferentstepsalongmRNAmetabolism:alternativesplicingandtranslation.WealsorevealedAktasanSRproteinkinasecapableofphosphorylatingtheseSRproteins.WefoundthattheSRproteinSRSF1enhancesSUMOconjugationtoseveraltargetproteins,includingAkt.Here,thefurtherexploredthisunexpectedpost-translationalmodificationofAkt.BysitedirectedmutagenesiswemappedSUMOconjugationsiteswithinAkt.WefoundthatAktSUMOylationisrequiredforitsregulatoryroleonfibronectinandBcl-xaltrnativesplicing.Consistentwiththepro-survivalandpro-proliferativeroleofthiskinase,weshowedthatitsSUMOylationfavorstheproductionoffibronectinmRNAisoformscharacteristicofhighlyproliferativetissuesandtumors,aswellasofanti-apoptoticBcl-xmRNAisoforms.WealsofoundthatSUMOylationofAktcontrolsitsfunctionasaregulatorofcellcycleprogression.ThesefindingsrevealanovellevelofregulationforAktfunction,openingnewareasofexplorationrelatedtothemolecularmechanismsdeterminingthattheactivationofasinglekinasecanleadtoavastdiversityofcellularresponses.
