lncRNANBR2engagesametaboliccheckpointbyregulatingAMPKunderenergystressXiaowenLiu1,8,Zhen-DongXiao1,8,LengHan7,JiexinZhang2,Szu-WeiLee3,4,WenqiWang1,HyeminLee1,LiZhuang1,JunjieChen1,4,Hui-KuanLin3,4,5,6,JingWang2,HanLiang2,andBoyiGan1,3,4,91DepartmentofExperimentalRadiationOncology,theUniversityofTexasMDAndersonCancerCenter,1515HolcombeBlvd,Houston,Texas77030,USA2DepartmentofBioinformaticsandComputationalBiology,theUniversityofTexasMDAndersonCancerCenter,1515HolcombeBlvd,Houston,Texas77030,USA3DepartmentofMolecularandCellularOncology,theUniversityofTexasMDAndersonCancerCenter,1515HolcombeBlvd,Houston,Texas77030,USA4ProgramofGenesandDevelopment,andProgramofCancerBiology,theUniversityofTexasGraduateSchoolofBiomedicalSciences,1515HolcombeBlvd,Houston,Texas77030,USA5DepartmentofCancerBiology,WakeForestSchoolofMedicine,Winston-Salem,NorthCarolina27157,USA6GraduateInstituteofBasicMedicalScience,ChinaMedicalUniversity,Taichung404,Taiwan7DepartmentofBiochemistryandMolecularBiology,TheUniversityofTexasHealthScienceCenteratHoustonMcGovernMedicalSchool,Houston,Texas,77030AbstractLongnoncodingRNAs(lncRNAs)haveemergedascriticalregulatorsinvariouscellularprocesses.However,thepotentialinvolvementoflncRNAsinkinasesignalingremainslargelyunknown.AMP-activatedproteinkinase(AMPK)actsasacriticalsensorofcellularenergystatus.HereweshowthatlncRNANBR2(neighborofBRCA1gene2)isinducedbytheLKB1-AMPKpathwayunderenergystress.Uponenergystress,NBR2inturninteractswithAMPKandpromotesAMPKkinaseactivity,thusformingafeed-forwardlooptopotentiateAMPKactivationduringenergystress.DepletionofNBR2attenuatesenergystress-inducedAMPKactivation,resultinginuncheckedcellcycling,alteredapoptosis/autophagyresponse,andincreasedtumorUsersmayview,print,copy,anddownloadtextanddata-minethecontentinsuchdocuments,forthepurposesofacademicresearch,subjectalwaystothefullConditionsofuse:http://www.nature.com/authors/editorial_policies/license.html#terms9CorrespondenceshouldbeaddressedtoB.G.(;Email:bgan@mdanderson.org)8Theseau...
