dRASSF与Hippo的相互作用及其功能研究-豆柴文库

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dRASSF与Hippo的相互作用及其功能研究
Introduction:
DrosophilaRASSF,abbreviatedasdRASSF,isamemberoftheRASSFfamilyofproteinsandishighlyconservedacrossdifferentspecies,includinghumans.TheRASSFfamilyofproteinshasbeenextensivelystudiedinrecentyears,andanumberoffunctionsandroleshavebeenidentified.Inparticular,interactionsbetweendRASSFandtheHippopathwayhavebeenfoundtoplayacriticalroleinthemaintenanceoftissuehomeostasis.
TheHippopathwayisahighlyconservedpathwaythatregulatesorgansizeandgrowth.ItwasfirstidentifiedinDrosophilaandhassincebeenfoundtobeconservedinmammalsaswell.TheHippopathwayregulatestheactivityoftranscriptionfactors,suchasYapandTaz,byphosphorylatingthemandpromotingtheirdegradation.Thispathwayisactivatedbydifferentsignals,includingcelldensity,extracellularmatrixstiffness,andmechanicalforces.
dRASSFInteractionswiththeHippoPathway:
ThereareseveralpointsofinteractionbetweendRASSFandtheHippopathway,asshowninFigure1.ThefirstpointofinteractionisbetweendRASSFandthekinaseWarts(Wts).WtsisakeydownstreamcomponentoftheHippopathway,anditskinaseactivityisessentialfortheregulationofYki(thehomologofYapandTaz)activity.IthasbeenshownthatdRASSFcanenhancethekinaseactivityofWtsbybindingtoitdirectly.ThisinteractionoccursthroughtheN-terminalSARAHdomainofdRASSFandtheC-terminalSARAHdomainofWts.
AnotherpointofinteractionbetweendRASSFandtheHippopathwayisthroughthescaffoldproteinSalvador(Sav).SavalsointeractswithWtsandpromotesitskinaseactivity,andithasbeenshownthatdRASSFcanbindtoSavdirectlythroughitsN-terminaldomain.ThisinteractionbetweendRASSFandSavcanstrengthentheinteractionbetweenSavandWts,leadingtoincreasedkinaseactivity.
Lastly,dRASSFhasbeenfoundtointeractwiththekinaseHippo(Hpo)directlyaswell.ThisinteractionoccursthroughtheN-terminalSARAHdomainofdRASSFandtheC-terminalSARAHdomainofHpo.Althoughthepreciseroleofthisinteractionisnotyetclear,ithasbeensuggestedthatdRASSFmayserveasascaffoldproteintobringHpoandWtsintocloseproximity.
FunctionsofdRASSF-HippoPathwayInteractions:
TheinteractionsbetweendRASSFand